https://wiki.oroboros.at/api.php?action=feedcontributions&user=Bufe+Anja&feedformat=atomBioblast - User contributions [en]2024-03-28T22:14:24ZUser contributionsMediaWiki 1.36.1https://wiki.oroboros.at/index.php?title=Wohlfarter_Yvonne&diff=137337Wohlfarter Yvonne2017-06-16T11:12:15Z<p>Bufe Anja: </p>
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<div>{{Person<br />
|lastname=Wohlfarter<br />
|firstname=Yvonne<br />
|institution=::::::::::::::::::::[[File:WohlfarterY.JPG|right|150px|Yvonne Wohlfarter]] <br />
'''OROBOROS INSTRUMENTS'''<br />
:: Mitochondria and cell research<br />
'''Trainee'''<br />
:* [[FEMtech Internship for students|FEMtech Internship for students]]<br />
<br />
Yvonne Wohlfarter has been collaborating with [[OROBOROS_Contact |OROBOROS]] since June 2016 and completed an internship as a trainee from 2016-06-24 to 2016-09-23 and from 2017-06-01 to 2017-08-11.<br />
|address=Schöpfstr. 18<br />
|area code=6020<br />
|city=Innsbruck<br />
|country=Austria<br />
|mailaddress=Yvonne.Wohlfarter@gmx.at<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bufe_A&diff=136210Bufe A2017-06-02T14:17:00Z<p>Bufe Anja: </p>
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<div>{{EAGLE<br />
|COST= Member<br />
|COST WG1= WG1 <br />
|COST WG4= WG4}}<br />
{{Person<br />
|lastname=Bufe<br />
|firstname=Anja<br />
|title=MSc.<br />
|institution=:::::::::::::::[[File:BufeA.JPG|right|150px|Anja Bufe]] <br />
'''OROBOROS INSTRUMENTS'''<br />
:: Mitochondria and cell research<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' Metabolic profiles in normal, dysplastic and cancerous oral cells<br />
<br />
Anja Bufe joined [[OROBOROS_Contact |OROBOROS]] in March 2017.<br />
|address=Schöpfstrasse 18<br />
|area code=A-6020<br />
|city=Innsbruck<br />
|country=Austria<br />
|mailaddress=anja.bufe@oroboros.at<br />
|weblink=http://wiki.oroboros.at/index.php/TRACT<br />
}}<br />
{{Labelingperson<br />
|field of research=Basic<br />
|topics=[[High-resolution respirometry]], cancer metabolism, oesophageal cancer,<br />
}}<br />
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<br />
[[Image:TRACT logo.png|right|170px|link=http://wiki.oroboros.at/index.php/TRACT]]<br />
[[Image:Marie Curie.jpg|right|170px|link=https://ec.europa.eu/research/mariecurieactions/]]<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Anja started her Marie Skłodowska-Curie PhD Fellowship with [[OROBOROS INSTRUMENTS]] at the [https://www.i-med.ac.at/ Medical University Innsbruck], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Anja presented her project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==<br />
::::* [[TRACT Kick-off meeting Dublin IE| TRACT Kick-off meeting]]<br />
::::* [[MITOEAGLE_Barcelona_2017]]<br />
::::* [[MiPNet22.03 IOC119 Innsbruck AT| IOC119 Innsbruck AT]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=File:Hu_et_al_(2012)_Fig.2A.PNG&diff=136127File:Hu et al (2012) Fig.2A.PNG2017-06-02T09:07:36Z<p>Bufe Anja: Fig.2A from Hu et al (2012) showing experimental rationale of analyzing mitochondrial complex I and II activities and representative oxygen consumption curve of T-Rex-293 cells before and after K-ras induction for 48 h. The numbers indicate oxygen cons...</p>
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<div>Fig.2A from Hu et al (2012) showing experimental rationale of analyzing mitochondrial complex I and II activities and representative oxygen consumption curve of T-Rex-293 cells before and after K-ras induction for 48 h. The numbers indicate oxygen consumption rate (nmol/ml/min) of mitochondrial complex I to IV and II to IV. Arrows indicate the time points when reagents were added. Rotenone: 100 nM; digitonin: 30 μg/ml; succinate: 5 μM.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=File:1R;2Rot;3Dig;4S.png&diff=136126File:1R;2Rot;3Dig;4S.png2017-06-02T09:04:26Z<p>Bufe Anja: Protocol in intact cells from Hu et al (2012)</p>
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<div>Protocol in intact cells from Hu et al (2012)</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=McPartlin_C&diff=135598McPartlin C2017-05-22T22:40:12Z<p>Bufe Anja: </p>
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<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=McPartlin<br />
|firstname=Catherine<br />
|institution='''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]]'''<br />
:* Project manager<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=tract@tcd.ie<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=TRACT&diff=135597TRACT2017-05-22T22:36:37Z<p>Bufe Anja: </p>
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<div>{{Template:OROBOROS header page name}}<br />
<br />
<big><big>'''TRACT - Training in Cancer Mechanisms and Therapeutics'''</big></big><br />
<br />
[[Image:TRACT logo.png|right|170px|link=http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|link=https://ec.europa.eu/research/mariecurieactions/]]<br />
<br />
:[http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics '''TRACT'''] is an international, inter-sectoral, multi-disciplinary project providing Marie Skłodowska-Curie PhD Fellowships to early stage researchers (ESRs) with the potential to become the leaders of tomorrow in cancer research.<br />
<br />
__TOC__<br />
<br />
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== TRACT Marie Skłodowska-Curie Project - News and Events ==<br />
<br />
'''TRACT''' supports eleven PhD fellows to complete research projects in the three critical areas: biomarker discovery, molecular resistance mechanisms and metabolic transformation mechanisms.<br />
This will allow for the discovery of novel insights into the molecular and cellular basis of oral and oesophageal cancer and generate new diagnostic tools and therapeutics that will improve patient response and survival.<br /><br />
<br />
=== Web ===<br />
::::* [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT Website]<br />
::::* [https://twitter.com/TRACT_ITN Twitter: TRACT_ITN]<br />
<br />
=== Events ===<br />
::::* '''2017-03-27''' [[TRACT Kick-off meeting Dublin IE|Kick-off meeting Dublin]]<br />
::::* '''2017-06-26 - 2017-07-01''' [[MiPNet22.01 IOC122 Schroecken AT|OROBOROS O2k-Workshop on high-resolution respirometry (HRR) and O2k-Fluorometry Schroecken]]<br />
::::* '''2017-07-23 - 2017-07-30''' [[MiPschool Obergurgl 2017|10th MiPschool MITOEAGLE Obergurgl]]<br />
<br />
<br />
== TRACT: Call H2020-MSCA-ITN-2016 - Contents and Aims==<br />
<br />
=== Contents===<br />
:::: '''In 2012, 8.2 million people worldwide died of cancer, of which 5.3% or over half a million deaths were accounted for by oral and oesophageal cancer (OOC)'''<br />
:::: The European community requires early stage researchers (ESRs) trained in next-generation technologies for improved detection and treatment of oral and oesophageal cancers. The number of oral cancers diagnosed in the EU has increased by over 75% in the last 30 years, with long-term survival rates of only 50%. This is typically due to the late diagnosis of the disease and resistance to current therapies. Through the collaborative expertise of clinicians, biochemists, immunologists, and chemists TRACT will enable ESRs to discover novel insights into the molecular and cellular basis of these cancers and generate new diagnostic tools and therapeutics that improve patient response and survival. Each Institution brings unique but complementary expertise in cancer metabolism, metabolomics, high-resolution imaging, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development and translational medicine. Industrial placements in five European countries will ensure ESRs receive specialised training in the development of next-generation technologies in such areas as whole genome sequencing, CRISPR technology, drug screening, exosome isolation and analysis, cancer imaging, metabolism and metabolite analysis in addition to the unique employment experience of working in the private sector. Courses in commercialisation, project management and presentation skills will ensure ESRs will have the ability to present their results to the entire cross-section of the European community, through public engagement. <br />
<br />
<br />
=== Objectives ===<br />
<br />
:::: '''TRACT will provide ESRs with exposure to a collaborative network''' of European academic and industrial experts working in the complementary domains of cancer metabolism, metabolomics, high-resolution imaging, bioinformatics, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development, nanotechnology and translational medicine. Although there are many researchers working on OOC in the relevant domains listed above, there is a lack of integration between domains - through a programme of integrative training and research, TRACT will bring together relevant domains to deliver better diagnostics and therapeutics for OOC with the overall aim of improving patient response and survival.<br />
<br />
<br />
:::: '''TRACT will deliver a cohort of internationally mobile cancer researchers with interdisciplinary skills''' who will have enhanced career prospects and be in a position to have an impact on the European and global research stage by providing new technologies that can drive entrepreneurship into the European economy and improved diagnostics and treatment options for cancer patients in Europe and beyond. <br />
<br />
<br />
:::: The '''overall aim of the research programme''' is to integrate basic and applied research in three related themes in order to deliver new diagnostic & prognostic tools and therapeutic approaches for patients with OOC.<br />
<br />
:::: During the project, TRACT ESRs will undertake novel research to:<br />
:::: 1) Determine novel '''biomarkers''' at the protein, glycan and molecular level to enable early detection of OOC and to predict patient response to therapy.<br />
:::: 2) Uncover the molecular basis of '''drug resistance''' in OOC leading to the identification of new drug targets and the development of novel cancer therapeutics.<br />
:::: 3) Enhance knowledge of '''metabolic transformation''' in OOC leading to the identification of novel targets for therapeutic intervention.<br />
<br />
:::::::::::: [[Image:TRACT diagnosis and therapy neu.png|500px|TRACT Diagnosis and therapy]]<br />
<br />
<br />
=== Applications for TRACT PhD Positions ===<br />
<br />
:::: Total applications received: 150<br />
:::: Countries represented: 44<br />
:::: Application profiles: 34% were EU, 4% are candidate EU countries and 62% are non-EU applicants.<br />
:::: Gender balance: 59% women, 41 % men.<br />
:::: Appointed PhD students who will be starting in March: 11<br />
<br />
<br />
== TRACT Marie Skłodowska-Curie PhD Fellows and Supervisors ==<br />
<br />
<br />
{| class="wikitable sortable"<br />
|-<br />
! ESR !! Project title !! ESR name !! Host institution !! Supervisor(s) !! Workpackage<br />
|-<br />
| 1 || Inflammatory response elements and glycan profiles as salivary biomarkers for the early diagnosis of OSCC || [[Dikova V|Valentina Dikova]] || UVEG (Valencia, Spain) || [[Bagan J|Prof. Jose Bagan]] || <br />
Biomarker Discovery (WP2)<br />
|-<br />
| 2 || Identification of novel molecular biomarkers predictive of benefit to neo-adjuvant chemotherapy in OAC || [[Sutton E|Eilis Sutton]] || QUB (Belfast, United Kingdom) ||[[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Biomarker Discovery (WP2)<br />
|-<br />
| 3 || Modulation of salivary inflammatory markers in patients undergoing radiotherapy for OSCC || [[Principe S|Sara Principe]] || UVEG (Valencia, Spain) || [[Bagan J|Prof. Jose Bagan]] || Biomarker Discovery (WP2)<br />
|-<br />
| 4 || A pathways-based approach to identify determinants of drug resistance in OAC || [[McCabe N|Niamh McCabe]] || QUB (Belfast, United Kingdom) || [[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 5 || Inflammatory caspases as biomarkers for OAC? Determining the role of inflammatory caspases in OAC development and resistance || [[Flis E|Ewelina Flis]] || TCD (Dublin, Ireland) || [[Creagh E|Prof. Emma Creagh]] & [[Murray J|Dr. James Murray]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 6 || Mcl-1 inhibitors for the treatment of OSCC || [[Prashant S|Prashant Saraswati]] || UNISI (Siena, Italy) || [[Campiani G|Prof. Giuseppe Campiani]] & [[Butini_S|Stefania Butini]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 7 || HAMLET derivatives as a pre-operative therapy in OAC || [[Ghanim M|Magda Ghanim]] || TCD (Dublin, Ireland) || [[Hun Mok K|Prof. Ken Hun Mok]] & [[Kelly V|Dr. Vincent Kelly]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 8 || Development of novel autophagy modulators to improve sensitivity of OSCC to chemotherapy || [[Kahn T|Tuhina Kahn]] || UNISI (Siena, Italy) || [[Campiani G|Prof. Giuseppe Campiani]] & [[Butini_S|Stefania Butini]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 9 || Pre-clinical evaluation of targeting autophagy for the treatment of OSCC || [[Magnano_S|Stefania Magnano]] || TCD (Dublin, Ireland) || [[Zisterer_D|Prof. Daniela Zisterer]] & [[O’Sullivan J|Dr. Jeff O’Sullivan]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 10 || Metabolic profiles in normal, dysplastic and cancerous oral cells || [[Bufe_A|Anja Bufe]] || OROBOROS INSTRUMENTS (Innsbruck, Austria) || [[Gnaiger_E|Prof. Erich Gnaiger]] || Metabolic Transformation (WP4)<br />
|-<br />
| 11 || Mitochondrial function linked to metabolic differences in normal, dysplastic and cancerous oral cells || [[Karavyraki_M|Marilena Karavyraki]] || TCD (Dublin, Ireland) || [[Porter RK|Prof. Richard Porter]] || Metabolic Transformation (WP4)<br />
|}<br />
<br />
<br />
== ESR10 - Metabolic profiles in normal, dysplastic and cancerous oral cells (OROBOROS INSTRUMENTS / Medical University Innsbruck) ==<br />
'''[[Bufe A |Anja Bufe]]''' was selected as a PhD fellow and started her PhD project on the 2017-03-01 with OROBOROS INSTRUMENTS at the Medical University of Innsbruck, within the Marie Skłodowska-Curie Innovative Training Network TRACT.<br />
* Planned secondment: TCD (duration: 2x3 months, supervisor: Prof. Richard Porter) - measure metabolic flux through (a) glycolysis, (b) pentose phosphate pathway and (c) glutaminolysis using 2H/13C NMR.<br />
<br />
=== WP4: Metabolic transformation ===<br />
<br />
::::* '''High-resolution respirometry to assay real time bioenergetics and metabolism in oral cancer cells'''<br />
::::* '''Metabolic profiles of normal, dysplastic and cancerous oral cells'''<br />
::::* '''Comparison of oxygen consumption and extracellular proton flux, as metrics of metabolic flux in different cell types under normoxic and hypoxic conditions; correlate with chemotherapy sensitivity'''<br />
::::* '''Identify differential novel drug targets in the cancer cells'''<br />
<br />
:::: TRACT will examine metabolic transformation mechanisms in OOC with the aim of identifying new drug targets for future therapeutic development. Metabolic transformation is a universal property of tumour formation and is a rich source of targets for development of therapeutic interventions. ESR 10 (Oroboros recruit; TCD secondment) will further characterise the bioenergetic and metabolic differences in normal, dysplastic and cancerous oral cancer cells using the OROBOROS O2k-MultiSensor system. This approach will identify differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells. Factors that control mitochondrial dynamics in cancer cells have also emerged as possible therapeutic targets.<br />
:::: The dynamic structure of the mitochondria in mammalian cells is defined by the opposing forces of fission and fusion, but the regulation of these mitochondrial processes is poorly understood. This is an emerging area in cancer research where cutting-edge imaging technologies are merging with molecular and cellular biology techniques. Pilot studies performed by Porter in TCD have identified a key molecule involved in controlling mitochondrial abundance (namely SIRT3) as a determinant of drug resistance in some solid cancers. ESR 11 (TCD recruit; Oroboros secondment) will establish the relationship between mitochondrial abundance, morphology, functional proteins involved in mitochondrial dynamics and metabolic differences in normal, dysplastic and oral cancer cells. This new knowledge will lead to the identification of novel therapeutic targets.<br />
<br />
=== Selected publications ===<br />
:::* Schöpf B, Schäfer G, Weber A, Talasz H, Eder IE, Klocker H, Gnaiger E (2016) Oxidative phosphorylation and mitochondrial function differ between human prostate tissue and cultured cells. FEBS J. - [[Schoepf 2016 FEBS J |»Bioblast link«]]<br />
:::* Makrecka-Kuka M, Krumschnabel G, Gnaiger E (2015) High-resolution respirometry for simultaneous measurement of oxygen and hydrogen peroxide fluxes in permeabilized cells, tissue homogenate and isolated mitochondria. Biomolecules 5:1319-38. - [[Makrecka-Kuka 2015 Biomolecules |»Bioblast link«]]<br />
:::* Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E (2015) Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol 119:1210-8. - [[Harrison 2015 J Appl Physiol |»Bioblast link«]]<br />
:::* Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. OROBOROS MiPNet Publications, Innsbruck:80 pp. - [[Gnaiger 2014 MitoPathways |»Bioblast link«]]<br />
:::* Gnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. Scand J Med Sci Sports 25 (Suppl 4):126–34. - [[Gnaiger 2015 Scand J Med Sci Sports |»Bioblast link«]]<br />
:::* Kristiansen G, Hu J, Wichmann D, Stiehl DP, Rose M, Gerhardt J, Bohnert A, ten Haaf A, Moch H, Raleigh J, Varia MA, Subarsky P, Scandurra FM, Gnaiger E, Gleixner E, Bicker A, Gassmann M, Hankeln T, Dahl E, Gorr TA (2011) Endogenous myoglobin in breast cancer is hypoxia-inducible by alternate transcription and functions to impair mitochondrial activity: a role in tumor suppression? J Biol Chem 286:43417-28. - [[Kristiansen 2011 J Biol Chem |»Bioblast link«]]<br />
:::* [[Gnaiger E |''More than six'']]<br />
<br />
<br />
== Coordinators ==<br />
<br />
:::: TRACT project manager:<br />
::::: [[McPartlin C|Catherine McPartlin]]<br />
::::: [https://www.tcd.ie/ Trinity College Dublin] - IE<br />
<br />
:::: TRACT project coordinator: <br />
::::: [[Zisterer D|Dr Daniela Zisterer]]<br />
::::: [https://www.tcd.ie/ Trinity College Dublin] - IE<br />
<br />
:::: OROBOROS project manager: <br />
::::: [[Laner V|Mag. Verena Laner]]<br />
<br />
<br />
<br />
== Project partners ==<br />
<br />
::::* [https://www.tcd.ie/ Trinity College Dublin] - IE <br />
<br />
::::* [http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS OROBOROS INSTRUMENTS GmbH] – AT<br />
<br />
::::* [http://www.uv.es/ Universitat de València] - ES <br />
<br />
::::* [http://en.unisi.it/ Universitá degli studi di Siena] - IT <br />
<br />
::::* [http://www.qub.ac.uk/ The Queen’s University of Belfast] - UK<br />
<br />
<br />
<br />
[[Image:Trinity_College_Dublin.jpg|200px|Trinity College Dublin]]<br />
[[Image:Logo OROBOROS INSTRUMENTS.jpg|100px|link=http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS OROBOROS]]<br />
[[Image:Universitat_de_Valencia.png|80px|Universitat de València]] <br />
[[Image:Universita_degli_studi_di_Siena.png|100px|Università degli studi di Siena]] <br />
[[Image:The_Queen's_University_of_Belfast.png|200px|The Queen's University of Belfast]]<br />
<br />
<br />
=== Further partner organisations ===<br />
<br />
::::* [http://www.agilent.com/home/ Agilent Technologies] - UK <br />
::::* [https://www.almacgroup.com/diagnostics/ Almac Diagnostics] - UK <br />
::::* [http://www.andor.com/ Andor Technology PLC] - UK <br />
::::* [http://www.fraunhofer.de/ Fraunhofer-Gesellschaft] - DE <br />
::::* [http://hornonline.com/exosomics-siena-spa/ Horn international - Exosomics Siena S.p.A.] - IT<br />
::::* [http://www.nibrt.ie/ National Institute for Bioprocessing Research and Training] - IE <br />
::::* [http://www.opsona.com/ Opsona Therapeutics] - IE <br />
<br />
[[Image:Agilent-Technologies-logo.jpg|130px|Agilent Technologies]]<br />
[[Image:Almac_Logo_200x75.png|110px|Almac Diagnostics]]<br />
[[Image:Andor_logo_mini.png|110px|Andor Technology]]<br />
[[Image:Fraunhofer Gesellschaft neu.gif|140px|Fraunhofer Gesellschaft]]<br />
[[Image:Horn_international.jpeg|110px|Horn international - Exosomics Siena S.p.A.]]<br />
[[Image:Nibrt.jpg|110px|National Institute for Bioprocessing Research and Training]]<br />
[[Image:Opsona_therapeutics_logo.jpg|110px|Opsona Therapeutics]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Kahn_T&diff=135596Kahn T2017-05-22T22:34:39Z<p>Bufe Anja: Created page with "{{Person |lastname=Kahn |firstname=Tuhina |title= |institution= '''Università degli Studi di Siena''' :: Department of Biotechnology, Chemistry and Pharmacy '''PhD. Student''..."</p>
<hr />
<div>{{Person<br />
|lastname=Kahn<br />
|firstname=Tuhina<br />
|title=<br />
|institution=<br />
'''Università degli Studi di Siena'''<br />
:: Department of Biotechnology, Chemistry and Pharmacy<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' Development of novel autophagy modulators to improve sensitivity of OSCC to chemotherapy<br />
|address=Via Aldo Moro 2<br />
|area code=53100<br />
|city=Siena<br />
|country=Italy<br />
|mailaddress=<br />
}}<br />
{{Labelingperson}}<br />
[[Image:TRACT logo.png|right|170px|TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|Marie Skłodowska-Curie Action]]<br />
<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Tuhina started her Marie Skłodowska-Curie PhD Fellowship at the [https://www.unisi.it/ Università degli Studi di Siena], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Tuhina presented her project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Prashant_S&diff=135595Prashant S2017-05-22T22:32:23Z<p>Bufe Anja: </p>
<hr />
<div>{{Person<br />
|lastname=Saraswati<br />
|firstname=Prashant<br />
|title=<br />
|institution=<br />
'''Università degli Studi di Siena'''<br />
:: Department of Biotechnology, Chemistry and Pharmacy<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' Mcl-1 inhibitors for the treatment of OSCC<br />
|address=Via Aldo Moro 2<br />
|area code=53100<br />
|city=Siena<br />
|country=Italy<br />
|mailaddress=<br />
}}<br />
{{Labelingperson}}<br />
[[Image:TRACT logo.png|right|170px|TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|Marie Skłodowska-Curie Action]]<br />
<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Prashant started his Marie Skłodowska-Curie PhD Fellowship at the [https://www.unisi.it/ Università degli Studi di Siena], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Prashant presented his project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Prashant_S&diff=135594Prashant S2017-05-22T22:31:40Z<p>Bufe Anja: Created page with "{{Person |lastname=Saraswati |firstname=Prashant |title= |institution= '''Università degli Studi di Siena''' :: Department of Biotechnology, Chemistry and Pharmacy '''PhD. St..."</p>
<hr />
<div>{{Person<br />
|lastname=Saraswati<br />
|firstname=Prashant<br />
|title=<br />
|institution=<br />
'''Università degli Studi di Siena'''<br />
:: Department of Biotechnology, Chemistry and Pharmacy<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' Mcl-1 inhibitors for the treatment of OSCC<br />
|address=Via Aldo Moro 2<br />
|area code=53100<br />
|city=Siena<br />
|country=Italy<br />
|mailaddress=<br />
}}<br />
{{Labelingperson}}<br />
[[Image:TRACT logo.png|right|170px|TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|Marie Skłodowska-Curie Action]]<br />
<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Prashant started his Marie Skłodowska-Curie PhD Fellowship at the [https://www.unisi.it/ Università degli Studi di Siena], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Prashant presented his project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==<br />
::::* [[TRACT Kick-off meeting Dublin IE| TRACT Kick-off meeting]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=TRACT&diff=135593TRACT2017-05-22T22:11:26Z<p>Bufe Anja: </p>
<hr />
<div>{{Template:OROBOROS header page name}}<br />
<br />
<big><big>'''TRACT - Training in Cancer Mechanisms and Therapeutics'''</big></big><br />
<br />
[[Image:TRACT logo.png|right|170px|link=http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|link=https://ec.europa.eu/research/mariecurieactions/]]<br />
<br />
:[http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics '''TRACT'''] is an international, inter-sectoral, multi-disciplinary project providing Marie Skłodowska-Curie PhD Fellowships to early stage researchers (ESRs) with the potential to become the leaders of tomorrow in cancer research.<br />
<br />
__TOC__<br />
<br />
<br />
== TRACT Marie Skłodowska-Curie Project - News and Events ==<br />
<br />
'''TRACT''' supports eleven PhD fellows to complete research projects in the three critical areas: biomarker discovery, molecular resistance mechanisms and metabolic transformation mechanisms.<br />
This will allow for the discovery of novel insights into the molecular and cellular basis of oral and oesophageal cancer and generate new diagnostic tools and therapeutics that will improve patient response and survival.<br /><br />
<br />
=== Web ===<br />
::::* [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT Website]<br />
::::* [https://twitter.com/TRACT_ITN Twitter: TRACT_ITN]<br />
<br />
=== Events ===<br />
::::* '''2017-03-27''' [[TRACT Kick-off meeting Dublin IE|Kick-off meeting Dublin]]<br />
::::* '''2017-06-26 - 2017-07-01''' [[MiPNet22.01 IOC122 Schroecken AT|OROBOROS O2k-Workshop on high-resolution respirometry (HRR) and O2k-Fluorometry Schroecken]]<br />
::::* '''2017-07-23 - 2017-07-30''' [[MiPschool Obergurgl 2017|10th MiPschool MITOEAGLE Obergurgl]]<br />
<br />
<br />
== TRACT: Call H2020-MSCA-ITN-2016 - Contents and Aims==<br />
<br />
=== Contents===<br />
:::: '''In 2012, 8.2 million people worldwide died of cancer, of which 5.3% or over half a million deaths were accounted for by oral and oesophageal cancer (OOC)'''<br />
:::: The European community requires early stage researchers (ESRs) trained in next-generation technologies for improved detection and treatment of oral and oesophageal cancers. The number of oral cancers diagnosed in the EU has increased by over 75% in the last 30 years, with long-term survival rates of only 50%. This is typically due to the late diagnosis of the disease and resistance to current therapies. Through the collaborative expertise of clinicians, biochemists, immunologists, and chemists TRACT will enable ESRs to discover novel insights into the molecular and cellular basis of these cancers and generate new diagnostic tools and therapeutics that improve patient response and survival. Each Institution brings unique but complementary expertise in cancer metabolism, metabolomics, high-resolution imaging, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development and translational medicine. Industrial placements in five European countries will ensure ESRs receive specialised training in the development of next-generation technologies in such areas as whole genome sequencing, CRISPR technology, drug screening, exosome isolation and analysis, cancer imaging, metabolism and metabolite analysis in addition to the unique employment experience of working in the private sector. Courses in commercialisation, project management and presentation skills will ensure ESRs will have the ability to present their results to the entire cross-section of the European community, through public engagement. <br />
<br />
<br />
=== Objectives ===<br />
<br />
:::: '''TRACT will provide ESRs with exposure to a collaborative network''' of European academic and industrial experts working in the complementary domains of cancer metabolism, metabolomics, high-resolution imaging, bioinformatics, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development, nanotechnology and translational medicine. Although there are many researchers working on OOC in the relevant domains listed above, there is a lack of integration between domains - through a programme of integrative training and research, TRACT will bring together relevant domains to deliver better diagnostics and therapeutics for OOC with the overall aim of improving patient response and survival.<br />
<br />
<br />
:::: '''TRACT will deliver a cohort of internationally mobile cancer researchers with interdisciplinary skills''' who will have enhanced career prospects and be in a position to have an impact on the European and global research stage by providing new technologies that can drive entrepreneurship into the European economy and improved diagnostics and treatment options for cancer patients in Europe and beyond. <br />
<br />
<br />
:::: The '''overall aim of the research programme''' is to integrate basic and applied research in three related themes in order to deliver new diagnostic & prognostic tools and therapeutic approaches for patients with OOC.<br />
<br />
:::: During the project, TRACT ESRs will undertake novel research to:<br />
:::: 1) Determine novel '''biomarkers''' at the protein, glycan and molecular level to enable early detection of OOC and to predict patient response to therapy.<br />
:::: 2) Uncover the molecular basis of '''drug resistance''' in OOC leading to the identification of new drug targets and the development of novel cancer therapeutics.<br />
:::: 3) Enhance knowledge of '''metabolic transformation''' in OOC leading to the identification of novel targets for therapeutic intervention.<br />
<br />
:::::::::::: [[Image:TRACT diagnosis and therapy neu.png|500px|TRACT Diagnosis and therapy]]<br />
<br />
<br />
=== Applications for TRACT PhD Positions ===<br />
<br />
:::: Total applications received: 150<br />
:::: Countries represented: 44<br />
:::: Application profiles: 34% were EU, 4% are candidate EU countries and 62% are non-EU applicants.<br />
:::: Gender balance: 59% women, 41 % men.<br />
:::: Appointed PhD students who will be starting in March: 11<br />
<br />
<br />
== TRACT Marie Skłodowska-Curie PhD Fellows and Supervisors ==<br />
<br />
<br />
{| class="wikitable sortable"<br />
|-<br />
! ESR !! Project title !! ESR name !! Host institution !! Supervisor(s) !! Workpackage<br />
|-<br />
| 1 || Inflammatory response elements and glycan profiles as salivary biomarkers for the early diagnosis of OSCC || [[Dikova V|Valentina Dikova]] || UVEG (Valencia, Spain) || [[Bagan J|Prof. Jose Bagan]] || <br />
Biomarker Discovery (WP2)<br />
|-<br />
| 2 || Identification of novel molecular biomarkers predictive of benefit to neo-adjuvant chemotherapy in OAC || [[Sutton E|Eilis Sutton]] || QUB (Belfast, United Kingdom) ||[[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Biomarker Discovery (WP2)<br />
|-<br />
| 3 || Modulation of salivary inflammatory markers in patients undergoing radiotherapy for OSCC || [[Principe S|Sara Principe]] || UVEG (Valencia, Spain) || [[Bagan J|Prof. Jose Bagan]] || Biomarker Discovery (WP2)<br />
|-<br />
| 4 || A pathways-based approach to identify determinants of drug resistance in OAC || [[McCabe N|Niamh McCabe]] || QUB (Belfast, United Kingdom) || [[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 5 || Inflammatory caspases as biomarkers for OAC? Determining the role of inflammatory caspases in OAC development and resistance || [[Flis E|Ewelina Flis]] || TCD (Dublin, Ireland) || [[Creagh E|Prof. Emma Creagh]] & [[Murray J|Dr. James Murray]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 6 || Mcl-1 inhibitors for the treatment of OSCC || Prashant Saraswati || UNISI (Siena, Italy) || [[Campiani G|Prof. Giuseppe Campiani]] & [[Butini_S|Stefania Butini]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 7 || HAMLET derivatives as a pre-operative therapy in OAC || [[Ghanim M|Magda Ghanim]] || TCD (Dublin, Ireland) || [[Hun Mok K|Prof. Ken Hun Mok]] & [[Kelly V|Dr. Vincent Kelly]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 8 || Development of novel autophagy modulators to improve sensitivity of OSCC to chemotherapy || Tuhina Kahn || UNISI (Siena, Italy) || [[Campiani G|Prof. Giuseppe Campiani]] & [[Butini_S|Stefania Butini]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 9 || Pre-clinical evaluation of targeting autophagy for the treatment of OSCC || [[Magnano_S|Stefania Magnano]] || TCD (Dublin, Ireland) || [[Zisterer_D|Prof. Daniela Zisterer]] & [[O’Sullivan J|Dr. Jeff O’Sullivan]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 10 || Metabolic profiles in normal, dysplastic and cancerous oral cells || [[Bufe_A|Anja Bufe]] || OROBOROS INSTRUMENTS (Innsbruck, Austria) || [[Gnaiger_E|Prof. Erich Gnaiger]] || Metabolic Transformation (WP4)<br />
|-<br />
| 11 || Mitochondrial function linked to metabolic differences in normal, dysplastic and cancerous oral cells || [[Karavyraki_M|Marilena Karavyraki]] || TCD (Dublin, Ireland) || [[Porter RK|Prof. Richard Porter]] || Metabolic Transformation (WP4)<br />
|}<br />
<br />
<br />
== ESR10 - Metabolic profiles in normal, dysplastic and cancerous oral cells (OROBOROS INSTRUMENTS / Medical University Innsbruck) ==<br />
'''[[Bufe A |Anja Bufe]]''' was selected as a PhD fellow and started her PhD project on the 2017-03-01 with OROBOROS INSTRUMENTS at the Medical University of Innsbruck, within the Marie Skłodowska-Curie Innovative Training Network TRACT.<br />
* Planned secondment: TCD (duration: 2x3 months, supervisor: Prof. Richard Porter) - measure metabolic flux through (a) glycolysis, (b) pentose phosphate pathway and (c) glutaminolysis using 2H/13C NMR.<br />
<br />
=== WP4: Metabolic transformation ===<br />
<br />
::::* '''High-resolution respirometry to assay real time bioenergetics and metabolism in oral cancer cells'''<br />
::::* '''Metabolic profiles of normal, dysplastic and cancerous oral cells'''<br />
::::* '''Comparison of oxygen consumption and extracellular proton flux, as metrics of metabolic flux in different cell types under normoxic and hypoxic conditions; correlate with chemotherapy sensitivity'''<br />
::::* '''Identify differential novel drug targets in the cancer cells'''<br />
<br />
:::: TRACT will examine metabolic transformation mechanisms in OOC with the aim of identifying new drug targets for future therapeutic development. Metabolic transformation is a universal property of tumour formation and is a rich source of targets for development of therapeutic interventions. ESR 10 (Oroboros recruit; TCD secondment) will further characterise the bioenergetic and metabolic differences in normal, dysplastic and cancerous oral cancer cells using the OROBOROS O2k-MultiSensor system. This approach will identify differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells. Factors that control mitochondrial dynamics in cancer cells have also emerged as possible therapeutic targets.<br />
:::: The dynamic structure of the mitochondria in mammalian cells is defined by the opposing forces of fission and fusion, but the regulation of these mitochondrial processes is poorly understood. This is an emerging area in cancer research where cutting-edge imaging technologies are merging with molecular and cellular biology techniques. Pilot studies performed by Porter in TCD have identified a key molecule involved in controlling mitochondrial abundance (namely SIRT3) as a determinant of drug resistance in some solid cancers. ESR 11 (TCD recruit; Oroboros secondment) will establish the relationship between mitochondrial abundance, morphology, functional proteins involved in mitochondrial dynamics and metabolic differences in normal, dysplastic and oral cancer cells. This new knowledge will lead to the identification of novel therapeutic targets.<br />
<br />
=== Selected publications ===<br />
:::* Schöpf B, Schäfer G, Weber A, Talasz H, Eder IE, Klocker H, Gnaiger E (2016) Oxidative phosphorylation and mitochondrial function differ between human prostate tissue and cultured cells. FEBS J. - [[Schoepf 2016 FEBS J |»Bioblast link«]]<br />
:::* Makrecka-Kuka M, Krumschnabel G, Gnaiger E (2015) High-resolution respirometry for simultaneous measurement of oxygen and hydrogen peroxide fluxes in permeabilized cells, tissue homogenate and isolated mitochondria. Biomolecules 5:1319-38. - [[Makrecka-Kuka 2015 Biomolecules |»Bioblast link«]]<br />
:::* Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E (2015) Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol 119:1210-8. - [[Harrison 2015 J Appl Physiol |»Bioblast link«]]<br />
:::* Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. OROBOROS MiPNet Publications, Innsbruck:80 pp. - [[Gnaiger 2014 MitoPathways |»Bioblast link«]]<br />
:::* Gnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. Scand J Med Sci Sports 25 (Suppl 4):126–34. - [[Gnaiger 2015 Scand J Med Sci Sports |»Bioblast link«]]<br />
:::* Kristiansen G, Hu J, Wichmann D, Stiehl DP, Rose M, Gerhardt J, Bohnert A, ten Haaf A, Moch H, Raleigh J, Varia MA, Subarsky P, Scandurra FM, Gnaiger E, Gleixner E, Bicker A, Gassmann M, Hankeln T, Dahl E, Gorr TA (2011) Endogenous myoglobin in breast cancer is hypoxia-inducible by alternate transcription and functions to impair mitochondrial activity: a role in tumor suppression? J Biol Chem 286:43417-28. - [[Kristiansen 2011 J Biol Chem |»Bioblast link«]]<br />
:::* [[Gnaiger E |''More than six'']]<br />
<br />
<br />
== Coordinators ==<br />
<br />
:::: TRACT project manager:<br />
::::: [[McPartlin C|Catherine McPartlin]]<br />
::::: [https://www.tcd.ie/ Trinity College Dublin] - IE<br />
<br />
:::: TRACT project coordinator: <br />
::::: [[Zisterer D|Dr Daniela Zisterer]]<br />
::::: [https://www.tcd.ie/ Trinity College Dublin] - IE<br />
<br />
:::: OROBOROS project manager: <br />
::::: [[Laner V|Mag. Verena Laner]]<br />
<br />
<br />
<br />
== Project partners ==<br />
<br />
::::* [https://www.tcd.ie/ Trinity College Dublin] - IE <br />
<br />
::::* [http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS OROBOROS INSTRUMENTS GmbH] – AT<br />
<br />
::::* [http://www.uv.es/ Universitat de València] - ES <br />
<br />
::::* [http://en.unisi.it/ Universitá degli studi di Siena] - IT <br />
<br />
::::* [http://www.qub.ac.uk/ The Queen’s University of Belfast] - UK<br />
<br />
<br />
<br />
[[Image:Trinity_College_Dublin.jpg|200px|Trinity College Dublin]]<br />
[[Image:Logo OROBOROS INSTRUMENTS.jpg|100px|link=http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS OROBOROS]]<br />
[[Image:Universitat_de_Valencia.png|80px|Universitat de València]] <br />
[[Image:Universita_degli_studi_di_Siena.png|100px|Università degli studi di Siena]] <br />
[[Image:The_Queen's_University_of_Belfast.png|200px|The Queen's University of Belfast]]<br />
<br />
<br />
=== Further partner organisations ===<br />
<br />
::::* [http://www.agilent.com/home/ Agilent Technologies] - UK <br />
::::* [https://www.almacgroup.com/diagnostics/ Almac Diagnostics] - UK <br />
::::* [http://www.andor.com/ Andor Technology PLC] - UK <br />
::::* [http://www.fraunhofer.de/ Fraunhofer-Gesellschaft] - DE <br />
::::* [http://hornonline.com/exosomics-siena-spa/ Horn international - Exosomics Siena S.p.A.] - IT<br />
::::* [http://www.nibrt.ie/ National Institute for Bioprocessing Research and Training] - IE <br />
::::* [http://www.opsona.com/ Opsona Therapeutics] - IE <br />
<br />
[[Image:Agilent-Technologies-logo.jpg|130px|Agilent Technologies]]<br />
[[Image:Almac_Logo_200x75.png|110px|Almac Diagnostics]]<br />
[[Image:Andor_logo_mini.png|110px|Andor Technology]]<br />
[[Image:Fraunhofer Gesellschaft neu.gif|140px|Fraunhofer Gesellschaft]]<br />
[[Image:Horn_international.jpeg|110px|Horn international - Exosomics Siena S.p.A.]]<br />
[[Image:Nibrt.jpg|110px|National Institute for Bioprocessing Research and Training]]<br />
[[Image:Opsona_therapeutics_logo.jpg|110px|Opsona Therapeutics]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=TRACT&diff=135592TRACT2017-05-22T21:54:00Z<p>Bufe Anja: </p>
<hr />
<div>{{Template:OROBOROS header page name}}<br />
<br />
<big><big>TRACT - Training in Cancer Mechanisms and Therapeutics</big></big><br />
<br />
[[Image:TRACT logo.png|right|170px|link=http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|link=https://ec.europa.eu/research/mariecurieactions/]]<br />
<br />
:[http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics '''TRACT'''] supports eleven PhD fellows to complete research projects in the three critical areas: biomarker discovery, molecular resistance mechanisms and metabolic transformation mechanisms. This will allow for the discovery of novel insights into the molecular and cellular basis of oral and oesophageal cancer and generate new diagnostic tools and therapeutics that will improve patient response and survival.<br /><br />
:TRACT is an international, inter-sectoral, multi-disciplinary project providing Marie Skłodowska-Curie PhD Fellowships to early stage researchers (ESRs) with the potential to become the leaders of tomorrow in cancer research.<br />
<br />
__TOC__<br />
<br />
<br />
== TRACT Marie Skłodowska-Curie Project ==<br />
=== Web ===<br />
::::* [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT Website]<br />
::::* [https://twitter.com/TRACT_ITN Twitter: TRACT_ITN]<br />
<br />
=== Events ===<br />
::::* '''2017-03-27''' [[TRACT Kick-off meeting Dublin IE|Kick-off meeting Dublin]]<br />
::::* '''2017-06-26 - 2017-07-01''' [[MiPNet22.01 IOC122 Schroecken AT|OROBOROS O2k-Workshop on high-resolution respirometry (HRR) and O2k-Fluorometry Schroecken]]<br />
::::* '''2017-07-23 - 2017-07-30''' [[MiPschool Obergurgl 2017|10th MiPschool MITOEAGLE Obergurgl]]<br />
<br />
<br />
== TRACT: Call H2020-MSCA-ITN-2016 ==<br />
<br />
=== Contents===<br />
:::: '''In 2012, 8.2 million people worldwide died of cancer, of which 5.3% or over half a million deaths were accounted for by oral and oesophageal cancer (OOC)'''<br />
:::: The European community requires early stage researchers (ESRs) trained in next-generation technologies for improved detection and treatment of oral and oesophageal cancers. The number of oral cancers diagnosed in the EU has increased by over 75% in the last 30 years, with long-term survival rates of only 50%. This is typically due to the late diagnosis of the disease and resistance to current therapies. Through the collaborative expertise of clinicians, biochemists, immunologists, and chemists TRACT will enable ESRs to discover novel insights into the molecular and cellular basis of these cancers and generate new diagnostic tools and therapeutics that improve patient response and survival. Each Institution brings unique but complementary expertise in cancer metabolism, metabolomics, high-resolution imaging, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development and translational medicine. Industrial placements in five European countries will ensure ESRs receive specialised training in the development of next-generation technologies in such areas as whole genome sequencing, CRISPR technology, drug screening, exosome isolation and analysis, cancer imaging, metabolism and metabolite analysis in addition to the unique employment experience of working in the private sector. Courses in commercialisation, project management and presentation skills will ensure ESRs will have the ability to present their results to the entire cross-section of the European community, through public engagement. <br />
<br />
<br />
=== Objectives ===<br />
<br />
:::: '''TRACT will provide ESRs with exposure to a collaborative network''' of European academic and industrial experts working in the complementary domains of cancer metabolism, metabolomics, high-resolution imaging, bioinformatics, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development, nanotechnology and translational medicine. Although there are many researchers working on OOC in the relevant domains listed above, there is a lack of integration between domains - through a programme of integrative training and research, TRACT will bring together relevant domains to deliver better diagnostics and therapeutics for OOC with the overall aim of improving patient response and survival.<br />
<br />
<br />
:::: '''TRACT will deliver a cohort of internationally mobile cancer researchers with interdisciplinary skills''' who will have enhanced career prospects and be in a position to have an impact on the European and global research stage by providing new technologies that can drive entrepreneurship into the European economy and improved diagnostics and treatment options for cancer patients in Europe and beyond. <br />
<br />
<br />
:::: The '''overall aim of the research programme''' is to integrate basic and applied research in three related themes in order to deliver new diagnostic & prognostic tools and therapeutic approaches for patients with OOC.<br />
<br />
:::: During the project, TRACT ESRs will undertake novel research to:<br />
:::: 1) Determine novel '''biomarkers''' at the protein, glycan and molecular level to enable early detection of OOC and to predict patient response to therapy.<br />
:::: 2) Uncover the molecular basis of '''drug resistance''' in OOC leading to the identification of new drug targets and the development of novel cancer therapeutics.<br />
:::: 3) Enhance knowledge of '''metabolic transformation''' in OOC leading to the identification of novel targets for therapeutic intervention.<br />
<br />
:::::::::::: [[Image:TRACT diagnosis and therapy neu.png|500px|TRACT Diagnosis and therapy]]<br />
<br />
<br />
=== Applications for TRACT PhD Positions ===<br />
<br />
:::: Total applications received: 150<br />
:::: Countries represented: 44<br />
:::: Application profiles: 34% were EU, 4% are candidate EU countries and 62% are non-EU applicants.<br />
:::: Gender balance: 59% women, 41 % men.<br />
:::: Appointed PhD students who will be starting in March: 11<br />
<br />
<br />
== TRACT Marie Skłodowska-Curie PhD Fellows and Supervisors ==<br />
<br />
<br />
{| class="wikitable sortable"<br />
|-<br />
! ESR !! Project title !! ESR name !! Host institution !! Supervisor(s) !! Workpackage<br />
|-<br />
| 1 || Inflammatory response elements and glycan profiles as salivary biomarkers for the early diagnosis of OSCC || [[Dikova V|Valentina Dikova]] || UVEG (Valencia, Spain) || [[Bagan J|Prof. Jose Bagan]] || <br />
Biomarker Discovery (WP2)<br />
|-<br />
| 2 || Identification of novel molecular biomarkers predictive of benefit to neo-adjuvant chemotherapy in OAC || [[Sutton E|Eilis Sutton]] || QUB (Belfast, United Kingdom) ||[[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Biomarker Discovery (WP2)<br />
|-<br />
| 3 || Modulation of salivary inflammatory markers in patients undergoing radiotherapy for OSCC || [[Principe S|Sara Principe]] || UVEG (Valencia, Spain) || [[Bagan J|Prof. Jose Bagan]] || Biomarker Discovery (WP2)<br />
|-<br />
| 4 || A pathways-based approach to identify determinants of drug resistance in OAC || [[McCabe N|Niamh McCabe]] || QUB (Belfast, United Kingdom) || [[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 5 || Inflammatory caspases as biomarkers for OAC? Determining the role of inflammatory caspases in OAC development and resistance || [[Flis E|Ewelina Flis]] || TCD (Dublin, Ireland) || [[Creagh E|Prof. Emma Creagh]] & [[Murray J|Dr. James Murray]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 6 || Mcl-1 inhibitors for the treatment of OSCC || Prashant Saraswati || UNISI (Siena, Italy) || [[Campiani G|Prof. Giuseppe Campiani]] & [[Butini_S|Stefania Butini]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 7 || HAMLET derivatives as a pre-operative therapy in OAC || [[Ghanim M|Magda Ghanim]] || TCD (Dublin, Ireland) || [[Hun Mok K|Prof. Ken Hun Mok]] & [[Kelly V|Dr. Vincent Kelly]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 8 || Development of novel autophagy modulators to improve sensitivity of OSCC to chemotherapy || Tuhina Kahn || UNISI (Siena, Italy) || [[Campiani G|Prof. Giuseppe Campiani]] & [[Butini_S|Stefania Butini]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 9 || Pre-clinical evaluation of targeting autophagy for the treatment of OSCC || [[Magnano_S|Stefania Magnano]] || TCD (Dublin, Ireland) || [[Zisterer_D|Prof. Daniela Zisterer]] & [[O’Sullivan J|Dr. Jeff O’Sullivan]] || Resistance Mechanisms (WP3)<br />
|-<br />
| 10 || Metabolic profiles in normal, dysplastic and cancerous oral cells || [[Bufe_A|Anja Bufe]] || OROBOROS INSTRUMENTS (Innsbruck, Austria) || [[Gnaiger_E|Prof. Erich Gnaiger]] || Metabolic Transformation (WP4)<br />
|-<br />
| 11 || Mitochondrial function linked to metabolic differences in normal, dysplastic and cancerous oral cells || [[Karavyraki_M|Marilena Karavyraki]] || TCD (Dublin, Ireland) || [[Porter RK|Prof. Richard Porter]] || Metabolic Transformation (WP4)<br />
|}<br />
<br />
<br />
== ESR10 - Metabolic profiles in normal, dysplastic and cancerous oral cells (OROBOROS INSTRUMENTS / Medical University Innsbruck) ==<br />
'''[[Bufe A |Anja Bufe]]''' was selected as a PhD fellow and started her PhD project on the 2017-03-01 with OROBOROS INSTRUMENTS at the Medical University of Innsbruck, within the Marie Skłodowska-Curie Innovative Training Network TRACT.<br />
* Planned secondment: TCD (duration: 2x3 months, supervisor: Prof. Richard Porter) - measure metabolic flux through (a) glycolysis, (b) pentose phosphate pathway and (c) glutaminolysis using 2H/13C NMR.<br />
<br />
=== WP4: Metabolic transformation ===<br />
<br />
::::* '''High-resolution respirometry to assay real time bioenergetics and metabolism in oral cancer cells'''<br />
::::* '''Metabolic profiles of normal, dysplastic and cancerous oral cells'''<br />
::::* '''Comparison of oxygen consumption and extracellular proton flux, as metrics of metabolic flux in different cell types under normoxic and hypoxic conditions; correlate with chemotherapy sensitivity'''<br />
::::* '''Identify differential novel drug targets in the cancer cells'''<br />
<br />
:::: TRACT will examine metabolic transformation mechanisms in OOC with the aim of identifying new drug targets for future therapeutic development. Metabolic transformation is a universal property of tumour formation and is a rich source of targets for development of therapeutic interventions. ESR 10 (Oroboros recruit; TCD secondment) will further characterise the bioenergetic and metabolic differences in normal, dysplastic and cancerous oral cancer cells using the OROBOROS O2k-MultiSensor system. This approach will identify differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells. Factors that control mitochondrial dynamics in cancer cells have also emerged as possible therapeutic targets.<br />
:::: The dynamic structure of the mitochondria in mammalian cells is defined by the opposing forces of fission and fusion, but the regulation of these mitochondrial processes is poorly understood. This is an emerging area in cancer research where cutting-edge imaging technologies are merging with molecular and cellular biology techniques. Pilot studies performed by Porter in TCD have identified a key molecule involved in controlling mitochondrial abundance (namely SIRT3) as a determinant of drug resistance in some solid cancers. ESR 11 (TCD recruit; Oroboros secondment) will establish the relationship between mitochondrial abundance, morphology, functional proteins involved in mitochondrial dynamics and metabolic differences in normal, dysplastic and oral cancer cells. This new knowledge will lead to the identification of novel therapeutic targets.<br />
<br />
=== Selected publications ===<br />
:::* Schöpf B, Schäfer G, Weber A, Talasz H, Eder IE, Klocker H, Gnaiger E (2016) Oxidative phosphorylation and mitochondrial function differ between human prostate tissue and cultured cells. FEBS J. - [[Schoepf 2016 FEBS J |»Bioblast link«]]<br />
:::* Makrecka-Kuka M, Krumschnabel G, Gnaiger E (2015) High-resolution respirometry for simultaneous measurement of oxygen and hydrogen peroxide fluxes in permeabilized cells, tissue homogenate and isolated mitochondria. Biomolecules 5:1319-38. - [[Makrecka-Kuka 2015 Biomolecules |»Bioblast link«]]<br />
:::* Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E (2015) Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol 119:1210-8. - [[Harrison 2015 J Appl Physiol |»Bioblast link«]]<br />
:::* Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. OROBOROS MiPNet Publications, Innsbruck:80 pp. - [[Gnaiger 2014 MitoPathways |»Bioblast link«]]<br />
:::* Gnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. Scand J Med Sci Sports 25 (Suppl 4):126–34. - [[Gnaiger 2015 Scand J Med Sci Sports |»Bioblast link«]]<br />
:::* Kristiansen G, Hu J, Wichmann D, Stiehl DP, Rose M, Gerhardt J, Bohnert A, ten Haaf A, Moch H, Raleigh J, Varia MA, Subarsky P, Scandurra FM, Gnaiger E, Gleixner E, Bicker A, Gassmann M, Hankeln T, Dahl E, Gorr TA (2011) Endogenous myoglobin in breast cancer is hypoxia-inducible by alternate transcription and functions to impair mitochondrial activity: a role in tumor suppression? J Biol Chem 286:43417-28. - [[Kristiansen 2011 J Biol Chem |»Bioblast link«]]<br />
:::* [[Gnaiger E |''More than six'']]<br />
<br />
<br />
== Coordinators ==<br />
<br />
:::: TRACT project manager:<br />
::::: [[McPartlin C|Catherine McPartlin]]<br />
::::: [https://www.tcd.ie/ Trinity College Dublin] - IE<br />
<br />
:::: TRACT project coordinator: <br />
::::: [[Zisterer D|Dr Daniela Zisterer]]<br />
::::: [https://www.tcd.ie/ Trinity College Dublin] - IE<br />
<br />
:::: OROBOROS project manager: <br />
::::: [[Laner V|Mag. Verena Laner]]<br />
<br />
<br />
<br />
== Project partners ==<br />
<br />
::::* [https://www.tcd.ie/ Trinity College Dublin] - IE <br />
<br />
::::* [http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS OROBOROS INSTRUMENTS GmbH] – AT<br />
<br />
::::* [http://www.uv.es/ Universitat de València] - ES <br />
<br />
::::* [http://en.unisi.it/ Universitá degli studi di Siena] - IT <br />
<br />
::::* [http://www.qub.ac.uk/ The Queen’s University of Belfast] - UK<br />
<br />
<br />
<br />
[[Image:Trinity_College_Dublin.jpg|200px|Trinity College Dublin]]<br />
[[Image:Logo OROBOROS INSTRUMENTS.jpg|100px|link=http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS OROBOROS]]<br />
[[Image:Universitat_de_Valencia.png|80px|Universitat de València]] <br />
[[Image:Universita_degli_studi_di_Siena.png|100px|Università degli studi di Siena]] <br />
[[Image:The_Queen's_University_of_Belfast.png|200px|The Queen's University of Belfast]]<br />
<br />
<br />
=== Further partner organisations ===<br />
<br />
::::* [http://www.agilent.com/home/ Agilent Technologies] - UK <br />
::::* [https://www.almacgroup.com/diagnostics/ Almac Diagnostics] - UK <br />
::::* [http://www.andor.com/ Andor Technology PLC] - UK <br />
::::* [http://www.fraunhofer.de/ Fraunhofer-Gesellschaft] - DE <br />
::::* [http://hornonline.com/exosomics-siena-spa/ Horn international - Exosomics Siena S.p.A.] - IT<br />
::::* [http://www.nibrt.ie/ National Institute for Bioprocessing Research and Training] - IE <br />
::::* [http://www.opsona.com/ Opsona Therapeutics] - IE <br />
<br />
[[Image:Agilent-Technologies-logo.jpg|130px|Agilent Technologies]]<br />
[[Image:Almac_Logo_200x75.png|110px|Almac Diagnostics]]<br />
[[Image:Andor_logo_mini.png|110px|Andor Technology]]<br />
[[Image:Fraunhofer Gesellschaft neu.gif|140px|Fraunhofer Gesellschaft]]<br />
[[Image:Horn_international.jpeg|110px|Horn international - Exosomics Siena S.p.A.]]<br />
[[Image:Nibrt.jpg|110px|National Institute for Bioprocessing Research and Training]]<br />
[[Image:Opsona_therapeutics_logo.jpg|110px|Opsona Therapeutics]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Jeffrey_O%27Sullivan&diff=135591Jeffrey O'Sullivan2017-05-22T21:40:30Z<p>Bufe Anja: Redirected page to O’Sullivan J</p>
<hr />
<div>#REDIRECT [[O’Sullivan J]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bagan_J&diff=135590Bagan J2017-05-22T21:35:20Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Bagan |firstname=Jose |title=Prof. |institution='''University of Valencia''' :: Department of Stomatology ::..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Bagan<br />
|firstname=Jose<br />
|title=Prof.<br />
|institution='''University of Valencia'''<br />
:: Department of Stomatology<br />
:: Faculty of Medicine and Odontology<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=Gascó Oliag 1<br />
|area code=46010<br />
|city=Valencia<br />
|country=Spain<br />
|mailaddress=jose.v.bagan@uv.es <br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Kennedy_R&diff=135589Kennedy R2017-05-22T21:25:55Z<p>Bufe Anja: </p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Kennedy<br />
|firstname=Richard<br />
|title=Prof.<br />
|institution='''Queen's University Belfast'''<br />
:: School of Medicine, Dentistry and Biomedical Sciences,<br />
:: Centre for Cancer Research and Cell Biology,<br />
:: Institute for Health Sciences<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=97 Lisburn Road<br />
|area code=BT97BL<br />
|city=Belfast<br />
|country=United Kingdom<br />
|mailaddress=r.kennedy@qub.ac.uk<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Kennedy_R&diff=135588Kennedy R2017-05-22T21:25:39Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Kennedy |firstname=Richard |title=Prof. |institution='''Queen's University Belfast''' :: School of Medicine,..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Kennedy<br />
|firstname=Richard<br />
|title=Prof.<br />
|institution='''Queen's University Belfast'''<br />
:: School of Medicine, Dentistry and Biomedical Sciences,<br />
:: Centre for Cancer Research and Cell Biology<br />
:: Institute for Health Sciences,<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=97 Lisburn Road<br />
|area code=BT97BL<br />
|city=Belfast<br />
|country=United Kingdom<br />
|mailaddress=r.kennedy@qub.ac.uk<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Turkington_R&diff=135587Turkington R2017-05-22T21:23:56Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Turkington |firstname=Richard |title=Dr. |institution='''Queen's University Belfast''' :: School of Medicine..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Turkington<br />
|firstname=Richard<br />
|title=Dr.<br />
|institution='''Queen's University Belfast'''<br />
:: School of Medicine, Dentistry and Biomedical Sciences,<br />
:: Centre for Cancer Research and Cell Biology,<br />
:: Institute for Health Sciences<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=97 Lisburn Road<br />
|area code=BT97BL<br />
|city=Belfast<br />
|country=United Kingdom<br />
|mailaddress=r.turkington@qub.ac.uk<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Murray_J&diff=135586Murray J2017-05-22T21:15:05Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Murray |firstname=James |title=Dr. |institution='''Trinity College Dublin''' :: School of Biochemistry and I..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Murray<br />
|firstname=James<br />
|title=Dr.<br />
|institution='''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=james.murray@tcd.ie<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Creagh_E&diff=135585Creagh E2017-05-22T21:09:17Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Creagh |firstname=Emma |title=Dr. |institution='''Trinity College Dublin''' :: School of Biochemistry and Im..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Creagh<br />
|firstname=Emma<br />
|title=Dr.<br />
|institution='''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=ecreagh@tcd.ie <br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Kelly_V&diff=135584Kelly V2017-05-22T21:07:29Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Kelly |firstname=Vincent |title=Dr. |institution='''Trinity College Dublin''' :: School of Biochemistry and..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Kelly<br />
|firstname=Vincent<br />
|title=Dr.<br />
|institution='''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=kellyvp@tcd.ie <br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Hun_Mok_K&diff=135583Hun Mok K2017-05-22T21:00:58Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Hun Mok |firstname=Kenneth |title=Dr. |institution='''Trinity College Dublin''' :: School of Biochemistry an..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Hun Mok<br />
|firstname=Kenneth<br />
|title=Dr.<br />
|institution='''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=mok1@tcd.ie <br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Butini_S&diff=135582Butini S2017-05-22T20:49:38Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Butini |firstname=Stefania |title=PhD |institution='''Università degli Studi di Siena''' :: Department of B..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Butini<br />
|firstname=Stefania<br />
|title=PhD<br />
|institution='''Università degli Studi di Siena'''<br />
:: Department of Biotechnology, Chemistry and Pharmacy<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=Via Aldo Moro 2<br />
|area code=53100<br />
|city=Siena<br />
|country=Italy<br />
|mailaddress=butini3@unisi.it<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Campiani_G&diff=135581Campiani G2017-05-22T20:43:12Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=Campiani |firstname=Giuseppe |title=Prof. |institution='''Università degli Studi di Siena''' :: Department..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Campiani<br />
|firstname=Giuseppe<br />
|title=Prof.<br />
|institution='''Università degli Studi di Siena'''<br />
:: Department of Biotechnology, Chemistry and Pharmacy<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=Via Aldo Moro 2<br />
|area code=53100<br />
|city=Siena<br />
|country=Italy<br />
|mailaddress=giuseppe.campiani@unisi.it<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=O%E2%80%99Sullivan_J&diff=135580O’Sullivan J2017-05-22T20:30:19Z<p>Bufe Anja: Created page with "link=TRACT {{Person |lastname=O’Sullivan |firstname=Jeffrey |title=Dr. |institution='''Trinity College Dublin''' :: Dublin Dental Univer..."</p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=O’Sullivan<br />
|firstname=Jeffrey<br />
|title=Dr.<br />
|institution='''Trinity College Dublin'''<br />
:: Dublin Dental University Hospital<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=Lincoln Place 2<br />
|area code=D02VX37<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=josulli@tcd.ie<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Porter_RK&diff=135579Porter RK2017-05-22T20:18:24Z<p>Bufe Anja: </p>
<hr />
<div>[[Image:TRACT logo.png|right|170px|TRACT|link=TRACT]]<br />
{{EAGLE<br />
|COST= Member<br />
|COST WG1= WG1 <br />
|COST WG2= WG2<br />
|COST WG4= WG4 <br />
|COST Mentor= Mentor<br />
}}<br />
{{Person<br />
|lastname=Porter<br />
|firstname=Richard K<br />
|title=Prof. Dr.<br />
|institution=:::::::::::::::[[File:Richie.jpg|right|150px|Porter RK]]<br />
'''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]] supervisor'''<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=rkporter@tcd.ie<br />
}}<br />
{{Labelingperson<br />
|field of research=Basic, Veterinary<br />
}}<br />
<br />
==Participated at==<br />
::::* [[MITOEAGLE Barcelona 2017]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Zisterer_D&diff=135578Zisterer D2017-05-22T20:16:25Z<p>Bufe Anja: </p>
<hr />
<div>[[Image:TRACT logo.png|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Zisterer<br />
|firstname=Daniela<br />
|title=Prof.<br />
|institution='''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]]'''<br />
:* Project coordinator<br />
:* Supervisor<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=dzisterer@tcd.ie<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Zisterer_D&diff=135577Zisterer D2017-05-22T20:15:52Z<p>Bufe Anja: </p>
<hr />
<div>[[Image:TRACT logo.png|right|170px|TRACT|link=TRACT]]<br />
{{Person<br />
|lastname=Zisterer<br />
|firstname=Daniela<br />
|title=Prof.<br />
|institution='''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
'''[[TRACT|TRACT]]'''<br />
:* Project coordinator<br />
:* Supervisor<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=dzisterer@tcd.ie<br />
}}<br />
{{Labelingperson}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Porter_RK&diff=135576Porter RK2017-05-22T19:37:29Z<p>Bufe Anja: </p>
<hr />
<div>[[Image:TRACT logo.png|right|170px|TRACT|link=TRACT]]<br />
{{EAGLE<br />
|COST= Member<br />
|COST WG1= WG1 <br />
|COST WG2= WG2<br />
|COST WG4= WG4 <br />
|COST Mentor= Mentor<br />
}}<br />
{{Person<br />
|lastname=Porter<br />
|firstname=Richard K<br />
|title=Prof. Dr.<br />
|institution=:::::::::::::::[[File:Richie.jpg|right|150px|Porter RK]]<br />
'''Trinity College Dublin'''<br />
: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute (TBSI)<br />
|address=152-160 Pearse Street<br />
|area code=D02R590<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=rkporter@tcd.ie<br />
}}<br />
{{Labelingperson<br />
|field of research=Basic, Veterinary<br />
}}<br />
<br />
==Participated at==<br />
::::* [[MITOEAGLE Barcelona 2017]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Ghanim_M&diff=135575Ghanim M2017-05-22T19:12:48Z<p>Bufe Anja: </p>
<hr />
<div>{{Person<br />
|lastname=Ghanim<br />
|firstname=Magda<br />
|title=M.Sc.<br />
|institution=:::::::::::::::[[File:GhanimM.JPG|right|150px|Magda Ghanim]] <br />
'''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology,<br />
:: Trinity Biomedical Sciences Institute<br />
<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' HAMLET derivatives as a pre-operative therapy in oesophageal cancer<br />
|address=152-160 Pearse Street<br />
|area code=Dublin 2<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=mghanim@tde.ie<br />
}}<br />
{{Labelingperson}}<br />
[[Image:TRACT logo.png|right|170px|TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|Marie Skłodowska-Curie Action]]<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Magda started her Marie Skłodowska-Curie PhD Fellowship at the [https://www.tcd.ie/ Trinity College Dublin], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Magda presented her project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==<br />
::::* [[TRACT Kick-off meeting Dublin IE| TRACT Kick-off meeting]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Magnano_S&diff=135574Magnano S2017-05-22T19:01:24Z<p>Bufe Anja: </p>
<hr />
<div>{{Person<br />
|lastname=Magnano<br />
|firstname=Stefania<br />
|title=M.Sc.<br />
|institution=:::::::::::::::[[File:MagnanoStefania.png|right|150px|Stefania Magnano]] <br />
'''Trinity College Dublin'''<br />
:: School of Biochemistry and Immunology<br />
:: Trinity Biomedical Sciences Institute<br />
<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' Pre-clinical evaluation of targeting autophagy for the treatment of OSCC <br />
|address=152-160 Pearse Street<br />
|area code=Dublin 2<br />
|city=Dublin<br />
|country=Ireland<br />
|mailaddress=magnanos@tcd.ie<br />
}}<br />
{{Labelingperson}}<br />
[[Image:TRACT logo.png|right|170px|TRACT]]<br />
<br />
[[Image:Marie Curie.jpg|right|170px|Marie Skłodowska-Curie Action]]<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Stefania started her Marie Skłodowska-Curie PhD Fellowship at the [https://www.tcd.ie/ Trinity College Dublin], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Stefania presented her project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==<br />
::::* [[TRACT Kick-off meeting Dublin IE| TRACT Kick-off meeting]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=MiPschool_Obergurgl_2017&diff=135562MiPschool Obergurgl 20172017-05-22T14:50:50Z<p>Bufe Anja: </p>
<hr />
<div>{{MiP header page name}}<br />
{{Publication<br />
|title=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]]<br />
[[Image:MiPsocietyLOGO.JPG|right|120px|link=http://www.mitophysiology.org|MiPsociety]]<br />
'''Obergurgl AT''', 2017 Jul 23-30. '''10<sup>th</sup> MiP''school'' 2017 MITOEAGLE and MITOEAGLE Workshop WG1-4.<br />
|info=<br />
|authors=Mitochondrial Physiology Society<br />
|year=2017-07-23<br />
|journal=MitoGlobal<br />
|abstract='''2017 Jul 23-30, Obergurgl, AT.''' <br />
|mipnetlab=<br />
}}<br />
[[File:MUI Logo rz rgb.jpg|150px|right|link=https://www.i-med.ac.at |Medical University Innsbruck]]<br />
[[File:Logo_Univ_Innsbruck.jpg|100px|right|link=https://www.uibk.ac.at |University of Innsbruck]]<br />
[[File:Logo_age_reg.jpg|150px|right|link=https://www.uibk.ac.at/forschung/doktoratskollegs/index.html.de| DK Ageing and Regeneration]]<br />
<br />
__TOC__<br />
== Date, venue, organization ==<br />
::::* 2017 July 23-30<br />
:::::* 2017 July 23-27 Training School jointly organized by the [[Mitochondrial Physiology Society]] and [[MC_MITOEAGLE_e-VOTE_02#Topic_.282.29_Training_School_in_Obergurgl.2C_Tyrol.2C_AT_in_July_2017 |COST Action MITOEAGLE]]<br />
:::::* 2017 July 27-30 MITOEAGLE Workshop: [[MITOEAGLE_Working_Groups|WG1-4]]<br />
::::* [http://www.uz-obergurgl.at University Centre Obergurgl], Tyrol, Austria<br />
<br />
::::*[[MiPschool_Obergurgl_2017#Registration|Registration]] deadline: '''2017 May 31''' <br />
<br />
== Lecturers - preliminary list ==<br />
<br/><br />
<gallery mode=default perrow=5 widths="140px" heights="150px"><br />
File:Borutaite_V.jpg|'''[[Borutaite V|Borutaite Vilma]]'''<br />
File:DoerrierC.JPG|'''[[Doerrier Velasco CA|Doerrier Carolina]]'''<br />
File:Garcia-RovesP.jpg|'''[[Garcia-Roves PM |Garcia-Roves Pablo]]'''<br />
File:Gnaiger Erich.jpg|'''[[Gnaiger E|Gnaiger Erich]]'''<br />
File:Hoppel 2012x.jpg|'''[[Hoppel CL |Hoppel Charles L]]'''<br />
File:Pidder 2.jpg|'''[[Jansen-Duerr P |Jansen-Duerr Pidder]]'''<br />
File:Koopman WJH.JPG|'''[[Koopman WJ |Koopman Werner]]'''<br />
File:LeeHK.jpg|'''[[Lee HK |Lee Hong Kyu]]'''<br />
File:Moore Anthony L.jpg|'''[[Moore AL|Moore Anthony]]''' <br />
File:Carlos|'''[[Palmeira C |Palmeira Carlos]]'''<br />
File:Richie.jpg|'''[[Porter RK |Porter Richard K]]'''<br />
File:Velika B.jpg|'''[[Velika B |Velika Beata]]'''<br />
File:MiPs2015 14 Anthony Molina.jpg|'''[[Molina AJA |Molina Anthony]]'''<br />
</gallery><br />
<br />
== Programme ==<br />
<br />
:::: '''Programme development''': ''For the MiPsummer school in Obergurgl the last week of July, I would be delighted to come. I see you have me down for two presentations and you know that I always have a great time at the summer schools and meetings. The Retreat last year kept the tradition of great meetings with unbelievable and fantastic interactions. What can be better. I look forward to the details for travel, etc. My wife asked me how I would be able to turn down your invitation; no way.'' - '''[[Hoppel CL |Charles L Hoppel]]'''<br />
<br />
<br /><br />
[[File:Expand.png|right|45px |Click to expand or collaps]]<br />
<div class="toccolours mw-collapsible mw-collapsed"><br />
::: '''<big>» Programme structure</big>'''<br />
<div class="mw-collapsible-content"><br />
::::* '''2017-07-23, Day 1:''' Arrival<br />
::::* '''2017-07-24 to 26, Day 2-4: Training school MiP''society'' and MITOEAGLE''' <br />
::::** Day 2-3: Intoductory lectures on the mitochondrial electron transfer system (ETS), coupling of electron transfer to proton translocation and phosphorylation (OXPHOS), mitochondrial pathways, respiratory protocols for diagnosis of mitochondrial function, mitochondrial respiratory control in health and disease.<br />
::::** Day 4: Scientific lectures and student presentations<br />
::::* '''2017-07-27, Day 5:''' Departure Training school, arrival MITOEAGLE workshop, relaxing day for overall-participants<br />
::::* '''2017-07-28 to 29, Day 6-7: MITOEAGLE Workshop: WG1-4'''<br />
::::** '''WG1: Harmonization of nomenclature on mitochondrial respiratory states and control parameters:''' Status of the ''consensus paper'' on a consistent terminology on mitochondrial physiology and bioenergetics; recommendations for the use of a common terminology in mitochondrial physiological research as a milestone towards unification of concepts and nomenclature.<br />
::::** '''WG1: Respirometric reference protocols:''' (i) Standard format for presenting substrate-uncoupler-inhibitor titration (SUIT) protocols for a ‘library of protocols’ applied in mitochondrial respiratory physiology; (ii) criteria for selecting and recommending reference protocols; (iii) documentation of the state-of-the-art standards in designing, conducting, reporting, interpreting, and validating SUIT protocols (compare: Maelstrom Research program).<br />
::::** '''WG2-4: Data repositories'''<br />
::::* '''2017-07-30, Day 8:''' Departure MITOEAGLE<br />
</div><br />
</div><br />
<br /><br />
<br />
=== Preliminary programme MiP''school'' (Jul 23-27) ===<br />
<br />
::::* This MiP''school'' will focus on basic concepts on mitochondrial respiratory states and applications of substrate-uncoupler-inhibitor titration (SUIT) protocols. <br />
::::* [[Mitochondrial respiratory control: MITOEAGLE recommendations 1]]<br />
<br />
****: '''2017-07-24'''<br />
:::: '''Session A''' (morning) '''Introduction: coupling control in oxidative phosphorylation'''<br />
::::::* A1. The electron transfer system – Q redox regulation and mitochondrial pathways to oxygen ('''[[Moore AL |Anthony L Moore]]''', University of Sussex, UK).<br />
::::::* A2. Coupling of the phosphorylation system to electron transfer and respiratory coupling control ('''[[Borutaite V|Vilma Borutaite]]''', University of Health Sciences, LT).<br />
::::::* A3. From Einstein's diffusion equation to Mitchell’s chemiosmotic equation: rates and states in the bioenergetics of oxidative phosphorylation ('''[[Gnaiger E|Erich Gnaiger]]''', Medical University of Innsbruck, AT).<br />
::::::* A4. Biochemical coupling efficiency and ATP/O<sub>2</sub> ratios ('''[[Hoppel CL |Charles L Hoppel]]''', Case Western Reserve University School of Medicine, Ohio, US).<br />
<br />
:::: '''Session B''' (afternoon) '''Posters and selected abstracts'''<br />
::::::* B1. Poster session.<br />
::::::* B2: Selected abstracts: measurement of coupling control in intact cells and mitochondrial preparations - open discussion.<br />
::::::* B3. Towards a data base on coupling control in intact cells.<br />
<br />
****: '''2017-07-25'''<br />
:::: '''Session C''' (morning) '''Introduction: from experimental design to data analysis'''<br />
::::::* C1. Respiratory pathway control in mitochondrial preparations ('''[[Gnaiger E|Gnaiger Erich]]''', Medical University of Innsbruck, AT).<br />
::::::* C2. Substrate-uncoupler-inhibitor titration (SUIT) protocols – fundamental principles ('''[[Doerrier Velasco CA|Carolina Doerrier]]''', OROBOROS INSTRUMENTS, AT).<br />
::::::* C3. Normalization of respiratory flux and flow.<br />
::::::* C4. Respiratory control ratios and control factors ('''[[Gnaiger E|Gnaiger Erich]]''', Medical University of Innsbruck, AT).<br />
<br />
:::: '''Session D''' (afternoon) '''Posters and selected abstracts'''<br />
::::::* D1. Selected abstracts: applications of SUIT protocols – open discussion.<br />
::::::* D2. SUIT protocols: design and limitations.<br />
::::::* D3. Towards a data base on mitochondrial respiratory control: diagnostic approaches and comparative mitochondrial physiology.<br />
<br />
****: '''2017-07-26'''<br />
<br />
:::: '''Session E''' (morning) '''Comparative mitochondrial physiology''' (possible titles, depending on keynote lecturers/selected abstracts)<br />
::::::* E1. Mitochondrial physiology and the scope of cryopreservation in blood cells. ('''[[Velika B |Beata Velika]]''', Pavol Jozef Šafárik University in Kosice, SK) <br />
::::::* E2. Mitochondrial physiology studies in mouse models.<br />
::::::* E3. Mitochondrial vertrebrate physiology – extreme performers.<br />
::::::* E4. Mitochondrial physiology of and beyond established animal models.<br />
::::::* E5. Mitochondrial physiology in plants ('''[[Moore AL |Anthony L Moore]]''', University of Sussex, UK).<br />
::::::* E6. Mitochondrial physiology and evolution.<br />
<br />
:::: '''Session F''' (afternoon) '''Mitochondrial physiology: biomedical applications''' (possible titles, depending on keynote lecturers/selected abstracts)<br />
::::::* F1. The challenges of functional mitochondrial diagnosis ('''[[Hoppel CL |Charles L Hoppel]]''', Case Western Reserve University School of Medicine, Ohio, US).<br />
::::::* F2. Mitochondrial fitness in skeletal muscle ('''[[Garcia-Roves PM |Pablo Garcia-Roves]]''', University of Barcelona, ES).<br />
::::::* F3. Scope and limitations of functional mitochondrial diagnosis in blood cells. ('''[[Molina AJA |Anthony Molina]]''',Department of Internal Medicine, US). <br />
::::::* F4. Mitochondrial function and dysfunction: ROS and Ca<sup>2+</sup>. ('''[[Koopman WJ |Werner Koopman]]''', Radboud University Nijmegen Medical Centre, NL)<br />
::::::* F5. Mitochondrial function and dysfunction in cancer ('''[[Porter RK |Richard K Porter]]''', Trinity College Dublin, IE).<br />
::::::* F6. Ischemia-reperfusion injury ('''[[Palmeira C |Carlos Palmeira]]''', University of Coimbra, PT).<br />
::::::* F7. The metabolic syndrome - dysmitochondrial syndrome and mitochondrial disruptors ('''[[Lee HK |Hong Kyu Lee]]''', Eulji University College of Medicine, Seoul, KR).<br />
::::::* F8. Mitochondrial function in aging and regeneration ('''[[Jansen-Duerr P |Pidder Jansen-Duerr]]''', University of Innsbruck, AT). <br />
<br />
:::: '''Session G''' (evening) '''MITOEAGLE Early Career Investigators forum''' <br />
::::::* [[MITOEAGLE Early Career Investigators]]<br />
<br />
<br />
<br />
=== Preliminary programme MITOEAGLE Workshop WG1-4 (Jul 27-30) ===<br />
:::: currently in progress<br />
<br />
<br />
<br />
== Abstracts ==<br />
<br />
:::: Abstract submission: until '''May 31, 2017.'''<br />
:::: The abstract title has to be included on the registration form.<br />
<br />
:::* '''Categories''': Early career investigators (ECI) and students are invited to submit abstracts in five alternative categories and apply with their submission for a [[MiPschool_Obergurgl_2017#Support|MITOEAGLE Scholarship]]:<br />
<br />
::::# Your own project in the context of mitochondrial physiology.<br />
::::# SUIT protocols: basic concepts. - » [[MitoPedia: SUIT]] <br />
::::# SUIT protocols: various applications with intact cells and mt-preparations.<br />
::::# Definitions and controversies for a selected term on respiratory states and respiratory control ratios. - » [[MitoPedia: Respiratory states]], [[MitoPedia: Respiratory control ratios]]<br />
::::# Definition of a term in the context of mitochondrial physiology that is missing in MitoPedia. - » [[MitoPedia]]<br />
:::::: ''NOTE: If you have an idea or abstract in the context of mitochondrial research, that appears to not fit into one of the categories stated above, don't hesitate to contact us. We are open to new ideas!''<br />
<br />
:::* '''Format'''<br />
:::::: [[Abstract format]]<br />
:::::: '''Example''': [[Doerrier 2017 Abstract MITOEAGLE Barcelona]]<br />
<br />
<br />
:::* '''Abstract submission and review for MITOEAGLE Scholarships'''<br />
::::1. '''Eligibility:''' Early career investigators and students from all COST countries and International Partner Countries can apply - [[MITOEAGLE network]]. <br />
::::2. You need to select a 'Mentor' who will act as the contact to review your abstract and recommend you as a recipient of the MITOEAGLE scholarship.<br />
::::3. Check the [[MiPschool_Obergurgl_2017_Mentors|MITOEAGLE mentors website]] for the Training School, and select a 'Mentor'. <br />
::::4. Click on the highlighted name of the mentor for further details.<br />
::::::* Each mentor has two slots available. You can see in the column ''Booked'' whether the mentor is already booked or not. <br />
::::::*If you see that your preference no. 1 mentor already has one 'student', you might consider going for another mentor.<br />
::::5. Prepare your abstract in the format given above.<br />
::::::* Add the name of your selected mentor as a final section of your abstract.<br />
::::::* Cover letter: Provide a brief explanation to your selected mentor in a form of a cover letter.<br />
::::6. Send an Email to your mentor (and in Cc to mitoeagle@i-med.ac.at). Mention MITOEAGLE mentor in the subject line of your Email. Attach your abstract as a MS Word file and the cover letter.<br />
::::7. Experimental abstracts will be reviewed and accepted entirely independent of the experimental platform used in the study, and a wide variety of experimental approaches is highly welcome.<br />
<br />
::::» '''Notificiation of MITOEAGLE scholarships: 2017-06-10.'''<br />
<br />
<br />
== Support ==<br />
<br />
=== MITOEAGLE scholarships for Early Career Investigators and students ===<br />
<br />
::::* '''Submitted abstracts provide the basis for allocation of MITOEAGLE scholarships.<br />
::::* '''Proposed deadline: 2017-May-31'''.<br />
::::* '''42 basic scholarships''' will cover the local costs (accommodation, meals and registration). <br />
::::* Students from Inclusiveness Target Countries are eligible for '''extended scholarships''' covering travel costs in addition to the basic scholarship.<br />
<br />
::::* Abstracts submitted with data suitable for the data bases [[MITOEAGLE_Working_Groups|Working Groups 2, 3 and 4]] or [[WG1 MITOEAGLE protocols, terminology, documentation |Working Group 1]] are selected as a basis of additional support for joining the MITOEAGLE Workshop WG1-4 (Jul 27-30).<br />
::::* MITOEAGLE Working Group participants are supported (as far as possible) to join the Training School to be better prepared for the collaboration in the WG meeting, particularly the group working on the terminology review on respiratory states.<br />
<br />
::::» '''Notificiation of MITOEAGLE scholarships: 2017-06-10.'''<br />
<br />
=== Scholarships by the Medical University of Innsbruck ===<br />
<br />
::::* 10 students of the Medical University of Innsbruck will be supported by a scholarship. The scholarship will cover 80 % of the registration/accommodation costs.<br />
<br />
<br />
<br />
[[File:Questions.jpg|left|60px]] <br />
::::» For further questions, please contact the '''MITOEAGLE representatives of the training schools''': <br />
:::::: [[Schlattner U |Uwe Schlattner]]<br />
:::::: [[Engin AB |Ayse Basak Engin]]<br />
::::» Further details on mentorship: consult [[MITOEAGLE Early Career Investigators]]<br />
::::» [[MITOEAGLE_network#Members_in_the_MITOEAGLE_network |List of MITOEAGLE mentors]]<br />
<br />
<br />
<br />
=== ECTS for students of the Medical University of Innsbruck ===<br />
<br />
::::» For attending this conference, you will receive a credit of 1.5 ECTS.<br />
<br />
== Registration ==<br />
<br />
'''MiP''school'' registration Early Career Investigators and students'''<br />
::::» [[Media:Registration form Training School MITOEAGLE student.pdf| ECI and students registration]]<br />
<br />
::::» [[Media:Registration form Training School MITOEAGLE.pdf|Regular registration ]]<br />
<br />
<br />
'''MITOEAGLE Workshop WG1-4'''<br />
::::» [[Media:Registration_form_MITOEAGLE_Workshop_WG1-4.pdf|Registration form]]<br />
:::: Please send the completed form to [mailto:society@mitophysiology.org society@mitophysiology.org]<br />
<br />
<br />
== Travel info ==<br />
:::: How to get there? Find out more: [[MiPschool_Obergurgl_2017_Travel info|Travel info]]<br />
<br />
<br />
<br />
== Funding ==<br />
<br />
::::* [[COST Action MITOEAGLE |COST Action CA15203 Mitochondrial fitness mapping - MITOEAGLE]]<br />
<br />
[[Image:Tirol Logo Standortagentur.jpg|thumb|The project MitoFit is funded by the Land Tirol within the program K-Regio of Standortagentur Tirol.|left| 100px]]<br />
[[Image:Medizinische-Uni-Innsbruck-Logo.gif|100px| Medical University Innsbruck]]<br />
[[Image:MitoFit.jpg|80px|link=http://www.mitofit.org/index.php/K-Regio MitoFit|K-Regio MitoFit]]<br />
<br />
<br />
== 10 years ago ==<br />
::::» [[MiPschool Schroecken AT 2007]]<br />
<br />
<br />
<br />
[[Image:MitoGlobal.jpg|right|80px|link=MitoGlobal|MitoGlobal]] <br />
Listed under [[MitoGlobal Events]].<br />
<br />
<br />
{{MITOEAGLE banner}}<br />
{{Labeling<br />
|additional=2017, ORO, MitoFit, MITOEAGLE, Next<br />
}}</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bufe_A&diff=135474Bufe A2017-05-18T06:26:36Z<p>Bufe Anja: </p>
<hr />
<div>{{Person<br />
|lastname=Bufe<br />
|firstname=Anja<br />
|title=MSc.<br />
|institution=:::::::::::::::[[File:BufeA.JPG|right|150px|Anja Bufe]] <br />
'''OROBOROS INSTRUMENTS'''<br />
:: Mitochondria and cell research<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' Metabolic profiles in normal, dysplastic and cancerous oral cells<br />
<br />
Anja Bufe joined [[OROBOROS_Contact |OROBOROS]] in March 2017.<br />
|address=Schöpfstrasse 18<br />
|area code=A-6020<br />
|city=Innsbruck<br />
|country=Austria<br />
|mailaddress=anja.bufe@oroboros.at<br />
|weblink=http://wiki.oroboros.at/index.php/TRACT<br />
}}<br />
{{Labelingperson<br />
|field of research=Basic<br />
|topics=[[High-resolution respirometry]], cancer metabolism, oesophageal cancer,<br />
}}<br />
{{EAGLE<br />
|COST= Member<br />
|COST WG1= WG1 <br />
|COST WG4= WG4}}<br />
<br />
<br />
<br />
<br />
[[Image:TRACT logo.png|right|170px|link=http://wiki.oroboros.at/index.php/TRACT]]<br />
[[Image:Marie Curie.jpg|right|170px|link=https://ec.europa.eu/research/mariecurieactions/]]<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Anja started her Marie Skłodowska-Curie PhD Fellowship with [[OROBOROS INSTRUMENTS]] at the [https://www.i-med.ac.at/ Medical University Innsbruck], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Anja presented her project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==<br />
::::* [[TRACT Kick-off meeting Dublin IE| TRACT Kick-off meeting]]<br />
::::* [[MITOEAGLE_Barcelona_2017]]<br />
::::* [[MiPNet22.03 IOC119 Innsbruck AT| IOC119 Innsbruck AT]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bufe_A&diff=135473Bufe A2017-05-18T06:24:22Z<p>Bufe Anja: </p>
<hr />
<div>{{EAGLE<br />
|COST= Member<br />
|COST WG1= WG1 <br />
|COST WG4= WG4}}<br />
<br />
{{Person<br />
|lastname=Bufe<br />
|firstname=Anja<br />
|title=MSc.<br />
|institution=:::::::::::::::[[File:BufeA.JPG|right|150px|Anja Bufe]] <br />
'''OROBOROS INSTRUMENTS'''<br />
:: Mitochondria and cell research<br />
'''PhD. Student'''<br />
:* [[TRACT|TRACT]]<br />
:* '''Title of dissertation:''' Metabolic profiles in normal, dysplastic and cancerous oral cells<br />
<br />
Anja Bufe joined [[OROBOROS_Contact |OROBOROS]] in March 2017.<br />
<br />
<br />
|address=Schöpfstrasse 18<br />
|area code=A-6020<br />
|city=Innsbruck<br />
|country=Austria<br />
|mailaddress=anja.bufe@oroboros.at<br />
|weblink=http://wiki.oroboros.at/index.php/TRACT<br />
}}<br />
{{Labelingperson<br />
|field of research=Basic<br />
|topics=[[High-resolution respirometry]]<br />
}}<br />
<br />
[[Image:TRACT logo.png|right|170px|link=http://wiki.oroboros.at/index.php/TRACT]]<br />
[[Image:Marie Curie.jpg|right|170px|link=https://ec.europa.eu/research/mariecurieactions/]]<br />
<br />
== TRACT ==<br />
<br />
::::* '''2017-03-01''' Anja started her Marie Skłodowska-Curie PhD Fellowship with [[OROBOROS INSTRUMENTS]] at the [https://www.i-med.ac.at/ Medical University Innsbruck], supported by [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics/ TRACT] - Training in Cancer Mechanisms and Therapeutics.<br />
::::* '''2017-03-27''' Anja presented her project at the Kick-off meeting in Dublin for the first time in front of the TRACT core members and other TRACT PhD students<br />
<br />
<br />
== Participated at ==<br />
::::* [[TRACT Kick-off meeting Dublin IE| TRACT Kick-off meeting]]<br />
::::* [[MITOEAGLE_Barcelona_2017]]<br />
::::* [[MiPNet22.03 IOC119 Innsbruck AT| IOC119 Innsbruck AT]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Uncoupler&diff=135400Uncoupler2017-05-12T09:01:53Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=U<br />
|description=An '''uncoupler''' is a protonophore ([[CCCP]], [[FCCP]], [[DNP]]) which cycles across the inner mt-membrane with transport of protons and dissipation of the electrochemical proton gradient. Mild uncoupling may be induced at low uncoupler concentrations, the noncoupled state of [[ETS capacity]] is obtained at optimum uncoupler concentration for maximum flux, whereas at higher concentrations an uncoupler-induced inhibition is observed. <br />
» [[#Is_respiration_uncoupled_-_noncoupled_-_dyscoupled.3F |'''MiPNet article''']]<br />
|type=Chemicals<br />
}}<br />
{{MitoPedia methods|type=Chemicals<br />
}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Uncoupler<br />
|type=Chemicals<br />
}}<br />
<br />
[[File:Questions.jpg|left|40px]]<br />
<br /><br />
<div class="toccolours mw-collapsible mw-collapsed"><br />
::: <span style="font-size:105%; color:##424242">'''» Keywords'''</span><br />
<div class="mw-collapsible-content"><br />
::: '''Specific'''<br />
::::» [[Talk:Rogers_2011_PlosOne#Uncoupled_flux_does_not_reflect_electron_transfer_system_capacity|Artefacts by single dose uncoupling]]<br />
::::» [[ATP synthase]] <br />
::::» [[CCCP]]<br />
::::» [[Coupling control protocol]] <br />
::::» [[Talk:Uncoupler|Discussion: Uncoupler]]<br />
::::» [[DNP]]<br />
::::» [[Dyscoupled respiration]] <br />
::::» [[ETS capacity]] <br />
::::» [[ETS coupling efficiency]]<br />
::::» [[ETS state]] <br />
::::» [[FCCP]]<br />
::::» [[Noncoupled respiration]]<br />
::::» [[Optimum uncoupler concentration]]<br />
::::» [[ROUTINE control ratio]]<br />
::::» [[Uncoupler control ratio]]<br />
::::» [[Uncoupling proteins]]<br />
<br />
::: '''General'''<br />
::::» [[Adenine nucleotide translocase]]<br />
::::» [[Adenine_nucleotides|Adenylates]]<br />
::::» [[Cytochrome c release | Cytochrome ''c'' release]]<br />
::::» [[Electron transfer system]]<br />
::::» [[Flux control factor]]s<br />
::::» [[Flux control ratio]]s<br />
::::» [[Inhibitors]] <br />
::::» [[LEAK control ratio]]<br />
::::» [[LEAK respiration]] <br />
::::» [[Mitochondrial preparations]]<br />
::::» [[MiR06]]<br />
::::» [[OXPHOS]] <br />
::::» [[OXPHOS control ratio]]<br />
::::» [[Oxygen flux]]<br />
::::» [[Phosphorylation]] <br />
::::» [[Proton leak]]<br />
::::» [[Proton slip]]<br />
::::» [[Respiratory acceptor control ratio]]<br />
::::» [[ROUTINE respiration]]<br />
::::» [[ROUTINE state]] <br />
::::» [[State P]]'' <br />
::::» [[State 3]]<br />
::::» [[State 4]]<br />
::::» [[TIP2k]]<br />
</div><br />
</div><br />
<br /><br />
<br />
__TOC__<br />
= List of uncouplers =<br />
::::» [[MitoPedia: Uncouplers]]<br />
<br />
<br />
= Is respiration uncoupled - noncoupled - dyscoupled? =<br />
:::: or loosely coupled?<br />
{{Publication<br />
|title=Gnaiger E (2014) Is respiration uncoupled - noncoupled - dyscoupled? Mitochondr Physiol Network 2014-04-18.<br />
|info=<br />
|authors=OROBOROS<br />
|year=2014<br />
|journal=MiPNet<br />
|abstract=Coupling of [[OXPHOS]] represents a complex concept. '''Uncoupler''' titrations provide an invaluable experimental tool.<br />
|mipnetlab=AT Innsbruck Gnaiger E<br />
}}<br />
{{Labeling<br />
|topics=Coupling efficiency;uncoupling<br />
|couplingstates=LEAK, ETS<br />
|instruments=Theory<br />
}}<br />
== Uncoupled respiration ==<br />
<br />
:::: The '''uncoupled''' part of '''respiration''' in ''[[State P]]'' pumps protons to compensate for intrinsic uncoupling, which is a property of ('''''a''''') the inner mt-membrane ([[proton leak]]), ('''''b''''') the proton pumps ([[proton slip]]; decoupling), and ('''''c''''') is regulated by molecular uncouplers ([[uncoupling proteins]], UCP1). Uncoupled and [[dyscoupled respiration]] are summarized as [[LEAK respiration]]. In contrast, [[noncoupled respiration]] is induced [[optimum uncoupler concentration|experimentally]] for evaluation of [[ETS capacity]].<ref>Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45. [[Gnaiger 2009 Int J Biochem Cell Biol |»Bioblast link«]]</ref>,<ref>Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. OROBOROS MiPNet Publications, Innsbruck:80 pp. [[Gnaiger 2014 MitoPathways |»Bioblast link«]]</ref><br />
<br />
=== Uncoupled respiration - intrinsic ===<br />
:::: '''Uncoupling''' is used for ''intrinsic'' (physiological) uncoupling, appreciating the fact that we do not (never??) find mitochondria to be fully (mechanistically) coupled. In the [[ROUTINE]] (intact cells) and [[OXPHOS]] (mt-preparations) state of respiration, mitochondria are both, partially coupled and partially uncoupled. The uncoupled part of respiration in state ''P'' is larger than [[LEAK]] respiration evaluated in state ''L'' after inhibition of [[ATP synthase]] or [[adenine nucleotide translocase]]. This is due to the increase of mt-membrane potential in state ''L'' versus ''P'', causing a corresponding increase of the proton leak driven by the higher proton motive force. As an approximation, however, the difference ''E''-''L'' yields an estimate of the physiological scope of uncoupling, or the pathological scope of dyscoupling.<br />
<br />
=== Uncoupled respiration - experimental ===<br />
:::: '''Uncoupling''' is also used for directed experimental interventions to lower the degree of coupling, typically by application of established [[uncoupler]]s (experimental use of a pharmacological intervention), less typical by freeze-thawing or mechanical crashing of mitochondrial membranes. Such ''experimental'' uncoupling can induce stimulation or inhibition of respiration.<br />
<br />
=== Noncoupled respiration ===<br />
:::: '''[[Noncoupled respiration]]''' is distinguished from general (pharmacological or mechanical) uncoupled respiration, to give a label to an effort to reach the ''fully uncoupled'' (non-coupled) state without inhibiting respiration. Non-coupled respiration, therefore, yields an estimate of [[ETS capacity]]. Experimentally uncoupled respiration may fail to yield an estimate of ETS capacity, due to inhibition of respiration above optimum uncoupler concentrations or insufficient stimulation by sub-optimal uncoupler concentrations. '''[[Optimum uncoupler concentration]]s''' for evaluation of (noncoupled) ETS capacity require inhibitor titrations <ref>Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61. [[Steinlechner-Maran_1996_Am J Physiol Cell Physiol |»Bioblast link«]]</ref>,<ref> Hütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J 380: 919-928. [[Huetter_2004_Biochem J |»Bioblast link«]]</ref>,<ref> Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley:327-52. [[Gnaiger_2008_POS |»Bioblast link«]]</ref><br />
<br />
<br />
=== Dyscoupled respiration ===<br />
:::: '''[[Dyscoupled respiration]]''' is distinguished from intrinsically (physiologically) uncoupled and from extrinsic experimentally uncoupled respiration as an indication of ''extrinsic'' uncoupling (pathological, toxicological, pharmacological by agents that are not specifically applied to induce uncoupling, but are tested for their potential dyscoupling effect). Dyscoupling indicates a mitochondrial dysfunction. <ref> Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Mark W, Steurer W, Saks V, Usson Y, Margreiter R, Gnaiger E (2004) Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. Am J Physiol Heart Circ Physiol 286:H1633–41. [[Kuznetsov_2004_Am_J_Physiol_Heart_Circ_Physiol |»Bioblast link«]]</ref><br />
<br />
<br />
[[Talk:Uncoupler|Continue the discussion]]<br />
<br />
<br />
== Experimental ==<br />
<br />
=== Optimum uncoupler concentration ===<br />
:::: A titration of an uncoupler is necessary to achive the optimum concentration necessary for maximum stimulation of noncoupled respiration ([[ETS capacity]]) and to avoid inhibition of respiration by the too high uncoupler concentration. The underlying mechanism for the latter is not clear. <br />
<br />
:::: Uncouplers must be titrated carefully up to an optimum concentration for maximum stimulation of flux, since excess concentrations of uncoupler exert a strongly inhibitory effect.<br />
<br />
:::: See Steinlechner-Maran et al for a comparison of uncoupler titrations with [[FCCP]] and [[DNP]] from the [[ROUTINE state]] to the [[ETS state]] of cell respiration. <ref> Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61. [[Steinlechner-Maran_1996_Am J Physiol Cell Physiol |»Bioblast link«]]</ref> Uncoupler titrations after inhibition of respiration by oligomycin in the [[coupling control protocol]] with intact cells yield the sequence of [[ROUTINE respiration]], [[LEAK respiration]] and [[ETS capacity]], followed by inhibition to ROX. <ref>Hütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J 380:919-28. [[Huetter_2004_Biochem J |»Bioblast link«]]</ref>,<ref>Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley:327-52. [[Gnaiger_2008_POS |»Bioblast link«]]</ref> The highest accuracy of uncoupler titrations is achieved by titrations with the [[TIP2k]] at high concentrations of the stock solution. <ref>Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley:327-52. [[Gnaiger_2008_POS |»Bioblast link«]]</ref> Increasing the concentration in small steps, most accurately titrated by the [[TIP2k]], is recommended (0.5 or 0.25 µM steps or even smaller).<br />
<br />
:::: The optimum concentration of an uncoupler has to be determined for every biological system. It varies with incubation medium, sample concentratin, pharmacological treatment (with or without oligomycin), and pathophysiological state (e.g. induction of apoptosis). A single dose of uncoupler usually leads to an artefact in the estmation of maximum flux or electron transfer system capacity (for discussion, see [[Talk:Rogers_2011_PlosOne#Uncoupled_flux_does_not_reflect_electron_transfer_system_capacity|Artefacts by single dose uncoupling]]).<br />
<br />
:::: The optimum uncoupler (CCCP, FCCP, DNP) concentration for the noncoupled state varies over a large concentration range, depending on the medium ('binding' of uncoupler), type and concentration of sample. This is true for various uncouplers, such as CCCP, FCCP and DNP. <ref> Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61. [[Steinlechner-Maran_1996_Am J Physiol Cell Physiol |»Bioblast link«]]</ref> To evaluate the optimum concentration, a uncoupler titration has to be performed initially. For subsequent application series, we recommend a few titrations starting close to optimum concentration. <ref>Hütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J 380:919-28. [[Huetter_2004_Biochem J |»Bioblast link«]]</ref>,<ref>Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopisies of human muscle. Methods Mol Biol 810:25-58. [[Pesta 2012 Methods Mol Biol |»Bioblast link«]]</ref> Optimum CCCP or FCCP concentrations range over an order of magnitude, from <0.5 to >4.0 µM.<br />
<br />
=== Uncoupler titration ===<br />
:::: In '''uncoupler titrations''' various [[uncoupler]]s, such as CCCP, FCCP or DNP <ref>Fontana-Ayoub M, Fasching M, Gnaiger E (2014) Selected media and chemicals for respirometry with mitochondrial preparations. Mitochondr Physiol Network 03.02(17):1-9. [[MiPNet03.02 Chemicals-Media |»Bioblast link«]]</ref> are applied to uncouple mitochondrial electron transfer through Complexes I to IV from phosphorylation (Complex V or ATP synthase, ANT and phosphate transport), particularly with the aim to obtain the noncoupled [[state E]] with an [[optimum uncoupler concentration]] at maximum [[oxygen flux]].<br />
<br />
<br />
== Uncoupling control ratio, UCR ==<br />
:::: Uncouplers may be used not only in isolated mitochondria or permeabilized tissue preparations, but also in intact cells. Uncouplers are permeable through the cell membrane, and intact cells contain energy substrates for mitochondrial respiration. The noncoupled (uncoupler-activated) state may be compared with [[ROUTINE respiration]] of the intact cells, in terms of the ''R/E'' or [[ROUTINE control ratio]] (compare: [[uncoupler control ratio]], UCR). Or the non-coupled state may be the basis for evaluating [[LEAK respiration]] in the mitochondrial resting state induced by the addition of oligomycin (inhibitor of ATP synthase) or atractyloside (inhibitor of ANT), obtaing the ''L/E'' or LEAK control ratio (compare [[respiratory acceptor control ratio]], RCR).<br />
<br />
:::: There are strong mathematical arguments to replace the conventional UCR and [[RCR]] by the corresponding [[flux control factor]]s <ref>Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45. [[Gnaiger 2009 Int J Biochem Cell Biol |»Bioblast link«]]</ref>,<ref> Gnaiger E. Biochemical coupling efficiency: from 0 to <1. Mitochondr Physiol Network. »[[ETS coupling efficiency]]«</ref> and [[flux control ratio]]s.<br />
<br />
{|border="1"<br />
|1/UCR = [[ROUTINE respiration]] / Noncoupled respiration = ''R/E''; [[ROUTINE control ratio]]<br />
|-<br />
|Compare: ''L/E''; [[LEAK control ratio]]<br />
|-<br />
|Compare: ''P/E''; [[OXPHOS control ratio]]<br />
|}<br />
<br />
<br />
:::: When using uncouplers in [[mitochondrial preparations]] (mt-preparations: isolated mitochondria and permeabilized tissue or cells), different applications are distinguished:<br />
<br />
::::# External energy substrates have to be added to the preparation, since the endogenous substrates of the cytoplasm have been removed. A residual amount of internal mitochondrial substrates may be removed, if necessary, by an initial addition of a very small amount of ADP to the mitochondrial medium (e.g. [[MiR06]]) containing inorganic phosphate.<br />
::::# In mt-preparations, an uncoupler may be added as a methodological test for plasma membrane permeabilization. If the inital addition of ADP does not exert a stimulatory effect, subsequent addition of uncoupler will increase respiratory flux if permeabilization has not been achieved.<br />
::::# The classical respiratory control ratio ([[RCR]]=[[State 3]]/[[State 4]]) may be compared with an uncoupler-induced respiratory control ratio. Uncoupler titrations are initiated in a resting state, to induce an activated, noncoupled state. In the absence of [[adenylates]] (no ADP, ATP or AMP added), or in State 4 of isolated mitochondria (in the presence of ATP after phosphorylation of ADP), titration of uncoupler stimulates respiration. If [[OXPHOS]] has been initiated by the addition of a saturating concentration of ADP (which is different in isolated mitochondria versus permeabilized tissue or cell preparations), the experiment may be continued by addition of oligomycin or atractyloside, to return to a LEAK state, followed by uncoupler titration.<br />
::::# Respiratory flux in the noncoupled state is compared with [[OXPHOS]] (saturating ADP in the coupled state), to evaluate metabolic flux control by the phosphorylation system over the electron transfer capacity. Importantly, flux control by the phosphorylation system depends on the combination of [[MitoPedia: Substrates and metabolites|substrates]] and [[MitoPedia: Inhibitors|inhibitors]] applied to activate various segments of the [[electron transfer system]], and varies in different states of [[Cytochrome_c_control_factor#Cytochrome c release|cytochrome ''c'' release]].<br />
<br />
<br />
== References ==<br />
<references/><br />
* http://www.bmb.leeds.ac.uk/illingworth/oxphos/poisons.htm<br />
<br />
:::: »[[O2k-Publications: Coupling efficiency;uncoupling]]<br />
:::: »[[O2k-Publications: Instruments;methods]]<br />
<br />
<br />
== Related MitoPedia pages ==<br />
::* '''Electron transfer system, ETS'''<br />
::::» [[Electron transfer system]]<br />
::::» [[Q-junction]]<br />
<br />
::* '''Pathway control states'''<br />
::::» [[Pathway control state]]<br />
<br />
::* '''Coupling control state ''E'''''<br />
::::[[File:E.jpg |link=ETS capacity]] [[ETS capacity]]<br />
::::» [[Noncoupled respiration]]<br />
::::» [[Uncoupler#Is_respiration_uncoupled_-_noncoupled_-_dyscoupled.3F |Is respiration uncoupled - noncoupled - dyscoupled?]]<br />
<br />
[[Image:MiPMap Publication.jpg|left|120px|link=http://www.bioblast.at/index.php/MiPMap|Publications in the MiPMap]]<br />
<br /><br />
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::: <span style="font-size:105%; color:##424242">'''» List of publications: Uncoupler - Regulation and kinetics'''</span><br />
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::: <span style="font-size:105%; color:##424242">'''» List of publications: Uncoupler - ETS capacity'''</span><br />
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<br /></div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Uncoupler&diff=135399Uncoupler2017-05-12T09:00:34Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=U<br />
|description=An '''uncoupler''' is a protonophore ([[CCCP]], [[FCCP]], [[DNP]]) which cycles across the inner mt-membrane with transport of protons and dissipation of the electrochemical proton gradient. Mild uncoupling may be induced at low uncoupler concentrations, the noncoupled state of [[ETS capacity]] is obtained at optimum uncoupler concentration for maximum flux, whereas at higher concentrations an uncoupler-induced inhibition is observed. <br />
» [[#Is_respiration_uncoupled_-_noncoupled_-_dyscoupled.3F |'''MiPNet article''']]<br />
|type=Chemicals<br />
}}<br />
{{MitoPedia methods|type=Chemicals<br />
}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Uncoupler<br />
|type=Chemicals<br />
}}<br />
<br />
[[File:Questions.jpg|left|40px]]<br />
<br /><br />
<div class="toccolours mw-collapsible mw-collapsed"><br />
::: <span style="font-size:105%; color:##424242">'''» Keywords'''</span><br />
<div class="mw-collapsible-content"><br />
::: '''Specific'''<br />
::::» [[Talk:Rogers_2011_PlosOne#Uncoupled_flux_does_not_reflect_electron_transfer_system_capacity|Artefacts by single dose uncoupling]]<br />
::::» [[ATP synthase]] <br />
::::» [[CCCP]]<br />
::::» [[Coupling control protocol]] <br />
::::» [[Talk:Uncoupler|Discussion: Uncoupler]]<br />
::::» [[DNP]]<br />
::::» [[Dyscoupled respiration]] <br />
::::» [[ETS capacity]] <br />
::::» [[ETS coupling efficiency]]<br />
::::» [[ETS state]] <br />
::::» [[FCCP]]<br />
::::» [[Noncoupled respiration]]<br />
::::» [[Optimum uncoupler concentration]]<br />
::::» [[ROUTINE control ratio]]<br />
::::» [[Uncoupler control ratio]]<br />
::::» [[Uncoupling proteins]]<br />
<br />
::: '''General'''<br />
::::» [[Adenine nucleotide translocase]]<br />
::::» [[Adenine_nucleotides|Adenylates]]<br />
::::» [[Cytochrome c release | Cytochrome ''c'' release]]<br />
::::» [[Electron transfer system]]<br />
::::» [[Flux control factor]]s<br />
::::» [[Flux control ratio]]s<br />
::::» [[Inhibitors]] <br />
::::» [[LEAK control ratio]]<br />
::::» [[LEAK respiration]] <br />
::::» [[Mitochondrial preparations]]<br />
::::» [[MiR06]]<br />
::::» [[OXPHOS]] <br />
::::» [[OXPHOS control ratio]]<br />
::::» [[Oxygen flux]]<br />
::::» [[Phosphorylation]] <br />
::::» [[Proton leak]]<br />
::::» [[Proton slip]]<br />
::::» [[Respiratory acceptor control ratio]]<br />
::::» [[ROUTINE respiration]]<br />
::::» [[ROUTINE state]] <br />
::::» [[State P]]'' <br />
::::» [[State 3]]<br />
::::» [[State 4]]<br />
::::» [[TIP2k]]<br />
</div><br />
</div><br />
<br /><br />
<br />
__TOC__<br />
= List of uncouplers =<br />
::::» [[MitoPedia: Uncouplers]]<br />
<br />
<br />
= Is respiration uncoupled - noncoupled - dyscoupled? =<br />
:::: or loosely coupled?<br />
{{Publication<br />
|title=Gnaiger E (2014) Is respiration uncoupled - noncoupled - dyscoupled? Mitochondr Physiol Network 2014-04-18.<br />
|info=<br />
|authors=OROBOROS<br />
|year=2014<br />
|journal=MiPNet<br />
|abstract=Coupling of [[OXPHOS]] represents a complex concept. '''Uncoupler''' titrations provide an invaluable experimental tool.<br />
|mipnetlab=AT Innsbruck Gnaiger E<br />
}}<br />
{{Labeling<br />
|topics=Coupling efficiency;uncoupling<br />
|couplingstates=LEAK, ETS<br />
|instruments=Theory<br />
}}<br />
== Uncoupled respiration ==<br />
<br />
:::: The '''uncoupled''' part of '''respiration''' in ''[[State P]]'' pumps protons to compensate for intrinsic uncoupling, which is a property of ('''''a''''') the inner mt-membrane ([[proton leak]]), ('''''b''''') the proton pumps ([[proton slip]]; decoupling), and ('''''c''''') is regulated by molecular uncouplers ([[uncoupling proteins]], UCP1). Uncoupled and [[dyscoupled respiration]] are summarized as [[LEAK respiration]]. In contrast, [[noncoupled respiration]] is induced [[optimum uncoupler concentration|experimentally]] for evaluation of [[ETS capacity]].<ref>Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45. [[Gnaiger 2009 Int J Biochem Cell Biol |»Bioblast link«]]</ref>,<ref>Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. OROBOROS MiPNet Publications, Innsbruck:80 pp. [[Gnaiger 2014 MitoPathways |»Bioblast link«]]</ref><br />
<br />
=== Uncoupled respiration - intrinsic ===<br />
:::: '''Uncoupling''' is used for ''intrinsic'' (physiological) uncoupling, appreciating the fact that we do not (never??) find mitochondria to be fully (mechanistically) coupled. In the [[ROUTINE]] (intact cells) and [[OXPHOS]] (mt-preparations) state of respiration, mitochondria are both, partially coupled and partially uncoupled. The uncoupled part of respiration in state ''P'' is larger than [[LEAK]] respiration evaluated in state ''L'' after inhibition of [[ATP synthase]] or [[adenine nucleotide translocase]]. This is due to the increase of mt-membrane potential in state ''L'' versus ''P'', causing a corresponding increase of the proton leak driven by the higher proton motive force. As an approximation, however, the difference ''E''-''L'' yields an estimate of the physiological scope of uncoupling, or the pathological scope of dyscoupling.<br />
<br />
=== Uncoupled respiration - experimental ===<br />
:::: '''Uncoupling''' is also used for directed experimental interventions to lower the degree of coupling, typically by application of established [[uncoupler]]s (experimental use of a pharmacological intervention), less typical by freeze-thawing or mechanical crashing of mitochondrial membranes. Such ''experimental'' uncoupling can induce stimulation or inhibition of respiration.<br />
<br />
=== Noncoupled respiration ===<br />
:::: '''[[Noncoupled respiration]]''' is distinguished from general (pharmacological or mechanical) uncoupled respiration, to give a label to an effort to reach the ''fully uncoupled'' (non-coupled) state without inhibiting respiration. Non-coupled respiration, therefore, yields an estimate of [[ETS capacity]]. Experimentally uncoupled respiration may fail to yield an estimate of ETS capacity, due to inhibition of respiration above optimum uncoupler concentrations or insufficient stimulation by sub-optimal uncoupler concentrations. '''[[Optimum uncoupler concentration]]s''' for evaluation of (noncoupled) ETS capacity require inhibitor titrations <ref>Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61. [[Steinlechner-Maran_1996_Am J Physiol Cell Physiol |»Bioblast link«]]</ref>,<ref> Hütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J 380: 919-928. [[Huetter_2004_Biochem J |»Bioblast link«]]</ref>,<ref> Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley:327-52. [[Gnaiger_2008_POS |»Bioblast link«]]</ref><br />
<br />
<br />
=== Dyscoupled respiration ===<br />
:::: '''[[Dyscoupled respiration]]''' is distinguished from intrinsically (physiologically) uncoupled and from extrinsic experimentally uncoupled respiration as an indication of ''extrinsic'' uncoupling (pathological, toxicological, pharmacological by agents that are not specifically applied to induce uncoupling, but are tested for their potential dyscoupling effect). Dyscoupling indicates a mitochondrial dysfunction. <ref> Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Mark W, Steurer W, Saks V, Usson Y, Margreiter R, Gnaiger E (2004) Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. Am J Physiol Heart Circ Physiol 286:H1633–41. [[Kuznetsov_2004_Am_J_Physiol_Heart_Circ_Physiol |»Bioblast link«]]</ref><br />
<br />
<br />
[[Talk:Uncoupler|Continue the discussion]]<br />
<br />
<br />
== Experimental ==<br />
<br />
=== Optimum uncoupler concentration ===<br />
:::: A titration of an uncoupler is necessary to achive the optimum concentration necessary for maximum stimulation of noncoupled respiration ([[ETS capacity]]) and to avoid inhibition of respiration by the too high uncoupler concentration. The underlying mechanism for the latter is not clear. <br />
<br />
:::: Uncouplers must be titrated carefully up to an optimum concentration for maximum stimulation of flux, since excess concentrations of uncoupler exert a strongly inhibitory effect.<br />
<br />
:::: See Steinlechner-Maran et al for a comparison of uncoupler titrations with [[FCCP]] and [[DNP]] from the [[ROUTINE state]] to the [[ETS state]] of cell respiration. <ref> Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61. [[Steinlechner-Maran_1996_Am J Physiol Cell Physiol |»Bioblast link«]]</ref> Uncoupler titrations after inhibition of respiration by oligomycin in the [[coupling control protocol]] with intact cells yield the sequence of [[ROUTINE respiration]], [[LEAK respiration]] and [[ETS capacity]], followed by inhibition to ROX. <ref>Hütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J 380:919-28. [[Huetter_2004_Biochem J |»Bioblast link«]]</ref>,<ref>Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley:327-52. [[Gnaiger_2008_POS |»Bioblast link«]]</ref> The highest accuracy of uncoupler titrations is achieved by titrations with the [[TIP2k]] at high concentrations of the stock solution. <ref>Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley:327-52. [[Gnaiger_2008_POS |»Bioblast link«]]</ref> Increasing the concentration in small steps, most accurately titrated by the [[TIP2k]], is recommended (0.5 or 0.25 µM steps or even smaller).<br />
<br />
:::: The optimum concentration of an uncoupler has to be determined for every biological system. It varies with incubation medium, sample concentratin, pharmacological treatment (with or without oligomycin), and pathophysiological state (e.g. induction of apoptosis). A single dose of uncoupler usually leads to an artefact in the estmation of maximum flux or electron transfer system capacity (for discussion, see [[Talk:Rogers_2011_PlosOne#Uncoupled_flux_does_not_reflect_electron_transfer_system_capacity|Artefacts by single dose uncoupling]]).<br />
<br />
:::: The optimum uncoupler (CCCP, FCCP, DNP) concentration for the noncoupled state varies over a large concentration range, depending on the medium ('binding' of uncoupler), type and concentration of sample. This is true for various uncouplers, such as CCCP, FCCP and DNP. <ref> Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61. [[Steinlechner-Maran_1996_Am J Physiol Cell Physiol |»Bioblast link«]]</ref> To evaluate the optimum concentration, a uncoupler titration has to be performed initially. For subsequent application series, we recommend a few titrations starting close to optimum concentration. <ref>Hütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J 380:919-28. [[Huetter_2004_Biochem J |»Bioblast link«]]</ref>,<ref>Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopisies of human muscle. Methods Mol Biol 810:25-58. [[Pesta 2012 Methods Mol Biol |»Bioblast link«]]</ref> Optimum CCCP or FCCP concentrations range over an order of magnitude, from <0.5 to >4.0 µM.<br />
<br />
=== Uncoupler titration ===<br />
:::: In '''uncoupler titrations''' various [[uncoupler]]s, such as CCCP, FCCP or DNP <ref>Fontana-Ayoub M, Fasching M, Gnaiger E (2014) Selected media and chemicals for respirometry with mitochondrial preparations. Mitochondr Physiol Network 03.02(17):1-9. [[MiPNet03.02 Chemicals-Media |»Bioblast link«]]</ref> are applied to uncouple mitochondrial electron transfer through Complexes I to IV from phosphorylation (Complex V or ATP synthase, ANT and phosphate transport), particularly with the aim to obtain the noncoupled [[state E]] with an [[optimum uncoupler concentration]] at maximum [[oxygen flux]].<br />
<br />
<br />
== Uncoupling control ratio, UCR ==<br />
:::: Uncouplers may be used not only in isolated mitochondria or permeabilized tissue preparations, but also in intact cells. Uncouplers are permeable through the cell membrane, and intact cells contain energy substrates for mitochondrial respiration. The noncoupled (uncoupler-activated) state may be compared with [[ROUTINE respiration]] of the intact cells, in terms of the ''R/E'' or [[ROUTINE control ratio]] (compare: [[uncoupler control ratio]], UCR). Or the non-coupled state may be the basis for evaluating [[LEAK respiration]] in the mitochondrial resting state induced by the addition of oligomycin (inhibitor of ATP synthase) or atractyloside (inhibitor of ANT), obtaing the ''L/E'' or LEAK control ratio (compare [[respiratory acceptor control ratio]], RCR).<br />
<br />
:::: There are strong mathematical arguments to replace the conventional UCR and [[RCR]] by the corresponding [[flux control factor]]s <ref>Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45. [[Gnaiger 2009 Int J Biochem Cell Biol |»Bioblast link«]]</ref>,<ref> Gnaiger E. Biochemical coupling efficiency: from 0 to <1. Mitochondr Physiol Network. »[[ETS coupling efficiency]]«</ref> and [[flux control ratio]]s.<br />
<br />
{|border="1"<br />
|1/UCR = [[ROUTINE respiration]] / Noncoupled respiration = ''R/E''; [[ROUTINE control ratio]]<br />
|-<br />
|Compare: ''L/E''; [[LEAK control ratio]]<br />
|-<br />
|Compare: ''P/E''; [[OXPHOS control ratio]]<br />
|}<br />
<br />
<br />
:::: When using uncouplers in [[mitochondrial preparations]] (mt-preparations: isolated mitochondria and permeabilized tissue or cells), different applications are distinguished:<br />
<br />
::::# External energy substrates have to be added to the preparation, since the endogenous substrates of the cytoplasm have been removed. A residual amount of internal mitochondrial substrates may be removed, if necessary, by an initial addition of a very small amount of ADP to the mitochondrial medium (e.g. [[MiR06]]) containing inorganic phosphate.<br />
::::# In mt-preparations, an uncoupler may be added as a methodological test for plasma membrane permeabilization. If the inital addition of ADP does not exert a stimulatory effect, subsequent addition of uncoupler will increase respiratory flux if permeabilization has not been achieved.<br />
::::# The classical respiratory control ratio ([[RCR]]=[[State 3]]/[[State 4]]) may be compared with an uncoupler-induced respiratory control ratio. Uncoupler titrations are initiated in a resting state, to induce an activated, noncoupled state. In the absence of [[adenylates]] (no ADP, ATP or AMP added), or in State 4 of isolated mitochondria (in the presence of ATP after [[phosphorylation]] of ADP), titration of uncoupler stimulates respiration. If [[OXPHOS]] has been initiated by the addition of a saturating concentration of ADP (which is different in isolated mitochondria versus permeabilized tissue or cell preparations), the experiment may be continued by addition of oligomycin or atractyloside, to return to a LEAK state, followed by uncoupler titration.<br />
::::# Respiratory flux in the noncoupled state is compared with [[OXPHOS]] (saturating ADP in the coupled state), to evaluate metabolic flux control by the phosphorylation system over the electron transfer capacity. Importantly, flux control by the phosphorylation system depends on the combination of [[MitoPedia: Substrates and metabolites|substrates]] and [[MitoPedia: Inhibitors|inhibitors]] applied to activate various segments of the [[electron transfer system]], and varies in different states of [[Cytochrome_c_control_factor#Cytochrome c release|cytochrome ''c'' release]].<br />
<br />
<br />
== References ==<br />
<references/><br />
* http://www.bmb.leeds.ac.uk/illingworth/oxphos/poisons.htm<br />
<br />
:::: »[[O2k-Publications: Coupling efficiency;uncoupling]]<br />
:::: »[[O2k-Publications: Instruments;methods]]<br />
<br />
<br />
== Related MitoPedia pages ==<br />
::* '''Electron transfer system, ETS'''<br />
::::» [[Electron transfer system]]<br />
::::» [[Q-junction]]<br />
<br />
::* '''Pathway control states'''<br />
::::» [[Pathway control state]]<br />
<br />
::* '''Coupling control state ''E'''''<br />
::::[[File:E.jpg |link=ETS capacity]] [[ETS capacity]]<br />
::::» [[Noncoupled respiration]]<br />
::::» [[Uncoupler#Is_respiration_uncoupled_-_noncoupled_-_dyscoupled.3F |Is respiration uncoupled - noncoupled - dyscoupled?]]<br />
<br />
[[Image:MiPMap Publication.jpg|left|120px|link=http://www.bioblast.at/index.php/MiPMap|Publications in the MiPMap]]<br />
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<br /></div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Talk:Adenine_nucleotides&diff=135380Talk:Adenine nucleotides2017-05-10T17:58:09Z<p>Bufe Anja: Created page with "== Adenine nucleotides and the transfer of energy == The breaking of one phosphoanhydride bond releases 30.5 kJ/mol of energy. Thus, the dephosphorylation of the energy-rich..."</p>
<hr />
<div>== Adenine nucleotides and the transfer of energy ==<br />
<br />
The breaking of one phosphoanhydride bond releases 30.5 kJ/mol of energy. Thus, the dephosphorylation of the energy-rich [[ATP]] to [[ADP]] yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below).<br />
<br />
:* ATP + H<sub>2</sub>O → ADP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ADP + H<sub>2</sub>O → AMP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ATP + H<sub>2</sub>O → AMP + 2P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which [[ATP]] is created from [[ADP]] and a free [[phosphate]] is needed. This reaction can be carried out by the membrane embedded [[ATP synthase]] (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H<sup>+</sup>), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, [[fatty acid oxidation]], [[anaerobic]] respiration, active transport mechanisms across the cell membrane - e.g. in the [[electron transfer system]] -, and synthesis of macromolecules such as DNA.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135379Adenine nucleotides2017-05-10T17:57:25Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''', which are also sometimes referred to as adenosines or adenylates, are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer.<br />
}}<br />
{{MitoPedia concepts}}<br />
{{MitoPedia methods}}<br />
{{MitoPedia O2k and high-resolution respirometry}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides have the typical structure of nucleotides including the purine base adenine attached to a five-carbon sugar and one to three phosphate groups. The three best known members of this family are the purine nucleotides AMP, [[ADP]] and [[ATP]], which can be converted into each other by the addition or removal of one to two [[phosphate]] groups. This process stores and releases energy by the establishing or breaking of phosphate bonds and is thereby essential for energy transfer and supply of multiple cellular reactions, especially cellular respiration.<br />
To restore the energy, an endergonic reaction, in which [[ATP]] is created from [[ADP]] and a free [[phosphate]] is needed. This reaction can be carried out by the membrane embedded [[ATP synthase]] (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H<sup>+</sup>), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form a part of essential biomolecules of life such as, for example, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=LEAK_state_without_adenylates&diff=135371LEAK state without adenylates2017-05-09T17:59:35Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=''L''<sub>N</sub><br />
|description=[[File:L.jpg |link=LEAK respiration]] In the '''LEAK state without adenylates''', ''L''<sub>N</sub> (N for no adenylates), mitochondrial respiration is measured after addition of substrates, which decreases slowly to the [[LEAK state]] after oxidation of endogenous substrates with no [[adenylates]].<br />
|info=[[Gnaiger 2014 MitoPathways]]<br />
}}<br />
{{MitoPedia concepts<br />
|mitopedia concept=Respiratory state, Recommended<br />
}}<br />
{{MitoPedia topics<br />
|mitopedia topic=EAGLE<br />
}}<br />
Communicated by [[Gnaiger E]] 2010-10-21, edited 2014-07-04.<br />
[[File:LEAK_N.jpg|300px|thumb|LEAK respiration without adenylates, ''L''<sub>N</sub>.]]<br />
== The LEAK state of respiration: towards a concept-linked terminology of respiratory states ==<br />
::::» ''More details:'' [[LEAK respiration]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135370Adenine nucleotides2017-05-09T17:58:16Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''', which are also sometimes referred to as adenosines or adenylates, are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer.<br />
}}<br />
{{MitoPedia concepts}}<br />
{{MitoPedia methods}}<br />
{{MitoPedia O2k and high-resolution respirometry}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides have the typical structure of nucleotides including the purine base adenine attached to a five-carbon sugar and one to three phosphate groups. The three best known members of this family are the purine nucleotides AMP, [[ADP]] and [[ATP]], which can be converted into each other by the addition or removal of one to two [[phosphate]] groups. This process stores or releases energy and is thereby essential for energy transfer and supply of multiple cellular reactions. The breaking of one phosphoanhydride bond releases 30.5 kJ/mol of energy. Thus, the dephosphorylation of the energy-rich [[ATP]] to [[ADP]] yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below).<br />
<br />
:* ATP + H<sub>2</sub>O → ADP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ADP + H<sub>2</sub>O → AMP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ATP + H<sub>2</sub>O → AMP + 2P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which [[ATP]] is created from [[ADP]] and a free [[phosphate]] is needed. This reaction can be carried out by the membrane embedded [[ATP synthase]] (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H<sup>+</sup>), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, [[fatty acid oxidation]], [[anaerobic]] respiration, active transport mechanisms across the cell membrane - e.g. in the [[electron transfer system]] -, and synthesis of macromolecules such as DNA.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form a part of essential biomolecules of life such as, for example, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135369Adenine nucleotides2017-05-09T17:48:14Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''' are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer. Their structures comprise the purine base adenine, a five-carbon sugar and one to three phosphate groups.<br />
}}<br />
{{MitoPedia concepts}}<br />
{{MitoPedia methods}}<br />
{{MitoPedia O2k and high-resolution respirometry}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides, which are also sometimes referred to as adenosines or adenylates, have the typical structure of nucleotides but feature an additional adenine, which is attached to the ribose sugar moiety of the nucleotide. The three best known members of this family are the purine nucleotides AMP, [[ADP]] and [[ATP]], which can be converted into each other by the addition or removal of one to two [[phosphate]] groups. This process stores or releases energy and is thereby essential for energy transfer and supply of multiple cellular reactions. The breaking of one phosphoanhydride bond releases 30.5 kJ/mol of energy. Thus, the dephosphorylation of the energy-rich [[ATP]] to [[ADP]] yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below).<br />
<br />
:* ATP + H<sub>2</sub>O → ADP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ADP + H<sub>2</sub>O → AMP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ATP + H<sub>2</sub>O → AMP + 2P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which [[ATP]] is created from [[ADP]] and a free [[phosphate]] is needed. This reaction can be carried out by the membrane embedded [[ATP synthase]] (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H<sup>+</sup>), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, [[fatty acid oxidation]], [[anaerobic]] respiration, active transport mechanisms across the cell membrane - e.g. in the [[electron transfer system]] -, and synthesis of macromolecules such as DNA.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form a part of essential biomolecules of life such as, for example, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenylates&diff=135368Adenylates2017-05-09T17:45:45Z<p>Bufe Anja: Redirected page to Adenine nucleotides</p>
<hr />
<div>#REDIRECT [[Adenine nucleotides]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Phosphorylation_pathway&diff=135367Phosphorylation pathway2017-05-09T17:34:58Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=DT<br />
|description=[[File:Phosphorylation system.jpg|thumb|left|250px|From Gnaiger 2014 MitoPathways]]<br />
The '''phosphorylation system''' is the functional unit utilizing the protonmotive force to phosphorylate ADP (D) to ATP (T), and may be defined more specifically as the DT-phosphorylation system or '''DT-system'''. The DT-system consists of [[adenine nucleotide translocase]], [[phosphate carrier]], and [[ATP synthase]]. Mitochondrial [[adenylate kinase]], mt-[[creatine kinase]] and mt-[[hexokinase]] constitute extended components of the DT-phosphorylation system, controlling local AMP and ADP concentrations and forming [[metabolic channel]]s. Since substrate-level phosphorylation is involved in the TCA-cycle, the mtDT system includes succinyl-CoA synthase (GDP to GTP or ADP to ATP).<br />
|info=[[Gnaiger 2009 Int J Biochem Cell Biol]]<br />
}}<br />
{{MitoPedia concepts<br />
|mitopedia concept=MiP concept, SUIT concept<br />
}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Enzyme<br />
}}<br />
Communicated by [[Gnaiger E]] 2010-08-15, edited 2016-08-26.<br />
<br />
== OXPHOS and substrate level phosphorylation ==<br />
<br />
:::: [[OXPHOS capacity]], measured as oxygen flux in coupled, ADP- and Pi-saturated mitochondria in an [[Pathway control state|ETS-competent substrate state]], may be limited by the phosphorylation system capacity. Mitochondria are the location of the chemiosmotic DT-system, but additionally carry out substrate-level phosphorylation in the TCA-cycle at the step of [[succinyl-CoA synthase]], phosphorylating GDP to GTP or ADP to ATP (taken together as DT). This step must be considered in the mtDT-phosphorylation system. If succinate is externally added to mt-preparations, succinyl-CoA synthase is not involved. However, if succinate is formed in the mt-matrix from 2-oxoglutarate (alpha-ketoglutarate), substrate-level phosphorylation at succinyl-CoA synthase must be accounted for in the interpretation of P/O (P/O<sub>2</sub>) ratios.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenylate_nucleotide_translocase&diff=135366Adenylate nucleotide translocase2017-05-09T17:27:53Z<p>Bufe Anja: Redirected page to Adenine nucleotide translocase</p>
<hr />
<div>#REDIRECT [[Adenine nucleotide translocase]]</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135301Adenine nucleotides2017-05-08T13:12:55Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''' are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer. Their structures comprise the purine base adenine, a five-carbon sugar and one to three phosphate groups.(for further information see text below)}}<br />
<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides, which are also generally called adenosines or adenylates by some people, have the typical structure of nucleotides but feature an additional adenine, which is attached to the ribose sugar moiety of the nucleotide. The three most popular members of this family are the purine nucleotides AMP, [[ADP]] and [[ATP]], which can be converted into each other by the addition or removal of one to two [[phosphate]] groups. This process stores or releases energy and is thereby essential for energy transfer and supply of multiple cellular reactions. The breaking of one phosphoanhydride bond releases 7.3 kcal/mol of energy. With this the dephosphorylation of the energy-rich [[ATP]] to [[ADP]] yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below). The reaction is carried out by the enzyme [[adenylate kinase]] (ADK or myokinase).<br />
:* ATP + H<sub>2</sub>O → ADP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ADP + H<sub>2</sub>O → AMP + P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ATP + H<sub>2</sub>O → AMP + 2P<sub>i</sub> &emsp; &emsp; &emsp; ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which [[ATP]] is created from [[ADP]] and a free [[phosphate]] is needed. This reaction can be carried out by the membrane embedded [[ATP synthase]] (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H<sup>+</sup>), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, [[fatty acid oxidation]], [[anaerobic]] respiration, active transport mechanisms across the cell membrane - e.g. in the [[electron transfer system]] -, and synthesis of macromolecules such as DNA.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form essential biomolecules of life like for example deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135300Adenine nucleotides2017-05-08T13:11:35Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''' are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer. Their structures comprise the purine base adenine, a five-carbon sugar and one to three phosphate groups.(for further information see text below)}}<br />
<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides, which are also generally called adenosines or adenylates by some people, have the typical structure of nucleotides but feature an additional adenine, which is attached to the ribose sugar moiety of the nucleotide. The three most popular members of this family are the purine nucleotides AMP, [[ADP]] and [[ATP]], which can be converted into each other by the addition or removal of one to two [[phosphate]] groups. This process stores or releases energy and is thereby essential for energy transfer and supply of multiple cellular reactions. The breaking of one phosphoanhydride bond releases 7.3 kcal/mol of energy. With this the dephosphorylation of the energy-rich [[ATP]] to [[ADP]] yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below). The reaction is carried out by the enzyme [[adenylate kinase]] (ADK or myokinase).<br />
:* ATP + H2O → ADP + Pi &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ADP + H2O → AMP + Pi &emsp; &emsp; &emsp; ΔG = -30.5 kJ/mol<br />
:* ATP + H2O → AMP + 2Pi &emsp; &emsp; &emsp; ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which [[ATP]] is created from [[ADP]] and a free [[phosphate]] is needed. This reaction can be carried out by the membrane embedded [[ATP synthase]] (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H+), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, [[fatty acid oxidation]], [[anaerobic]] respiration, active transport mechanisms across the cell membrane -e.g. in the [[electron transfer system]]-, and synthesis of macromolecules such as DNA.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form essential biomolecules of life like for example deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135296Adenine nucleotides2017-05-08T12:57:11Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''' are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer. Their structures comprise the purine base adenine, a five-carbon sugar and one to three phosphate groups.(for further information see text below)}}<br />
<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides, which are also generally called adenosines or adenylates by some people, have the typical structure of nucleotides but feature an additional adenine, which is attached to the ribose sugar moiety of the nucleotide. The three most popular members of this family are the purine nucleotides AMP, [[ADP]] and [[ATP]], which can be converted into each other by the addition or removal of one to two [[phosphate]] groups. This process stores or releases energy and is thereby essential for energy transfer and supply of multiple cellular reactions. The breaking of one phosphoanhydride bond releases 7.3 kcal/mol of energy. With this the dephosphorylation of the energy-rich [[ATP]] to [[ADP]] yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below). The reaction is carried out by the enzyme [[adenylate kinase]] (ADK or myokinase).<br />
:* ATP + H2O → ADP + Pi : : : : : ΔG = -30.5 kJ/mol<br />
:* ADP + H2O → AMP + Pi : : : : : ΔG = -30.5 kJ/mol<br />
:* ATP + H2O → AMP + 2Pi : : : : ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which [[ATP]] is created from [[ADP]] and a free [[phosphate]] is needed. This reaction can be carried out by the membrane embedded [[ATP synthase]] (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H+), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, [[fatty acid oxidation]], [[anaerobic]] respiration, active transport mechanisms across the cell membrane -e.g. in the [[electron transfer system]]-, and synthesis of macromolecules such as DNA.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form essential biomolecules of life like for example deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135293Adenine nucleotides2017-05-08T12:44:55Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''' are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer. Their structures comprise the purine base adenine, a five-carbon sugar and one to three phosphate groups.(for further information see text below)}}<br />
<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides, which are also generally called adenosines or adenylates by some people, have the typical structure of nucleotides but feature an additional adenine, which is attached to the ribose sugar moiety of the nucleotide. The three most popular members of this family are the purine nucleotides AMP, ADP and ATP, which can be converted into each other by the addition or removal of one to two phosphate groups. This process stores or releases energy and is thereby essential for energy transfer and supply of multiple cellular reactions. The breaking of one phosphoanhydride bond releases 7.3 kcal/mol of energy. With this the dephosphorylation of the energy-rich ATP to ADP yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below). The reaction is carried out by the enzyme adenylate kinase (ADK or myokinase).<br />
:* ATP + H2O → ADP + Pi : : : : : ΔG = -30.5 kJ/mol<br />
:* ADP + H2O → AMP + Pi : : : : : ΔG = -30.5 kJ/mol<br />
:* ATP + H2O → AMP + 2Pi : : : : ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which ATP is created from ADP and a free phosphate is needed. This reaction can be carried out by the membrane embedded ATP synthase (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H+), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, beta oxidation, anaerobic respiration, active transport mechanisms across the cell membrane -e.g. in the electron transfer system-, and synthesis of macromolecules such as DNA.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form essential biomolecules of life like for example deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Adenine_nucleotides&diff=135292Adenine nucleotides2017-05-08T12:44:26Z<p>Bufe Anja: Created page with "{{MitoPedia |abbr=AN |description='''Adenine nucleotides''' are a group of organic molecules including AMP, ADP and ATP. These molecules present the major players of e..."</p>
<hr />
<div>{{MitoPedia<br />
|abbr=AN<br />
|description='''Adenine nucleotides''' are a group of organic molecules including AMP, [[ADP]] and [[ATP]]. These molecules present the major players of energy storage and transfer. Their structures comprise the purine base adenine, a five-carbon sugar and one to three phosphate groups.(for more details see text below)}}<br />
<br />
{{MitoPedia topics<br />
|mitopedia topic=Substrate and metabolite<br />
}}<br />
<br />
== Adenine nucleotides and energy transfer ==<br />
<br />
Adenine nucleotides, which are also generally called adenosines or adenylates by some people, have the typical structure of nucleotides but feature an additional adenine, which is attached to the ribose sugar moiety of the nucleotide. The three most popular members of this family are the purine nucleotides AMP, ADP and ATP, which can be converted into each other by the addition or removal of one to two phosphate groups. This process stores or releases energy and is thereby essential for energy transfer and supply of multiple cellular reactions. The breaking of one phosphoanhydride bond releases 7.3 kcal/mol of energy. With this the dephosphorylation of the energy-rich ATP to ADP yields a free energy of 30.5 kJ/mol or even 61 kJ/mol when two phosphate groups are released (as shown below). The reaction is carried out by the enzyme adenylate kinase (ADK or myokinase).<br />
:* ATP + H2O → ADP + Pi : : : : : ΔG = -30.5 kJ/mol<br />
:* ADP + H2O → AMP + Pi : : : : : ΔG = -30.5 kJ/mol<br />
:* ATP + H2O → AMP + 2Pi : : : : ΔG = -61 kJ/mol<br />
<br />
To restore the energy, an endergonic reaction, in which ATP is created from ADP and a free phosphate is needed. This reaction can be carried out by the membrane embedded ATP synthase (also called complex V). The energy which is used to generate ATP from ADP and Pi is hereby available in the form of hydrogen ions (H+), which are moved down an electrochemical gradient, e.g. from the intermembrane space into the mitochondrial matrix.<br />
<br />
ATP and the free energy, which can be stored or generated by its conversion into ADP and AMP, is useful in many cellular processes, especially cellular respiration. It serves as an energy source for glycolysis, photosynthesis, beta oxidation, anaerobic respiration, active transport mechanisms across the cell membrane -e.g. in the electron transfer system-, and synthesis of macromolecules such as DNA.<br />
<br />
== Nucleotides ==<br />
<br />
Nucleotides are organic molecules and are made up of three subunits: a nitrogenous base (purine or pyrimidine base), a five-carbon sugar (ribose or deoxyribose) and one to three phosphate groups. With this, in short, nucleotides are nucleosides with attached phosphate group(s).<br />
Nucleotides present the building blocks of nucleic acids and by this form essential biomolecules of life like for example deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).<br />
In addition, they make up components that play important roles in biochemical processes, namely nucleoside triphosphates (ATP, GTP, CTP and UTP), which can store and transfer energy (by the conversion of ATP to ADP), or cAMP and cGMP, which participate in cell signalling (cGMP and cAMP). Some nucleotides are also incorporated into important cofactors of enzymatic reactions, for example coenzyme A, FAD, FMN, NAD, and NADP+, and therefore serve essential cellular functions.</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Uncoupling_proteins&diff=135280Uncoupling proteins2017-05-08T12:11:39Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=UCP<br />
|description='''Uncoupling proteins''' (UCPs) are mitochondrial anion carrier proteins that can be found in the inner mitochondrial membranes of animals and plants. They can act as uncouplers by dissipating the proton electrochemical gradient ([[mitochondrial membrane potential]]), generated by the [[electron transfer system]] by pumping protons from the mitochondrial matrix to the mitochondrial intermembrane space.<br />
}}<br />
<br />
{{MitoPedia topics<br />
|mitopedia topic=Uncoupler<br />
}}<br />
<br />
== Uncoupling protein homologues ==<br />
<br />
The gene family of uncoupling proteins (UCP) includes five mitochondrial solute carriers 25 (SLC25), named UCP1 (SLC25A7), UCP2 (SLC25A48), UCP3 (SLC25A9), UCP4 (SLC25A27) and UCP5 (SLC25A14).<ref>Ramsden DB, Ho PW-L, Ho JW-M, Liu HF, So DHF, Tse HM, Chan KH, Ho SL (2012). Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain and Behavior. 2(4), 468–478.</ref>. These proteins have a tripartite structure and are located in the inner membrane of mitochondria. Presumably all of them contribute to the metabolic regulation elicited by cold exposure, including ROS and lipid metabolism, apoptosis and thermogenesis.<ref>Criscuolo F, Gonzalez‐Barroso MdM, Bouillaud F, Ricquier D, Miroux B, Sorci G (2005). Mitochondrial uncoupling proteins: New perspectives for evolutionary ecologists. The American Naturalist. 166(6):686-699.</ref> The thermogenic function of UCP1, which was the first uncoupling protein to be discovered in 1978 <ref>Nicholls DG, Bernson VSM, Heaton GM (1978). The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. In: Girardier L, Seydoux J, editors. Effectors of thermogenesis: Proceedings of a symposium held at geneva (switzerland) on 14 to 16 july 1977. Basel: Birkhäuser Basel. p. 89-93.</ref>, is already well established, whereas the exact functions of the closely related paralogues UCP2 and UCP3 are yet to be investigated. <ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiological Reviews. 84(1):277-359.</ref> <ref>Ricquier D, Bouillaud F (2000). The uncoupling protein homologues: Ucp1, ucp2, ucp3, stucp and atucp. Biochemical Journal. 345(2):161-179.</ref>. UCP4 and UCP5 are primarily expressed in the central nervous system (CNS) where they function as essential uncouplers of oxidative phosphorylation, thereby exerting an important protective function for cells by reducing oxidative stress (ROS).<br />
<br />
== Uncoupling protein 1 (UCP1) ==<br />
<br />
The uncoupling protein 1 (UCP1) is also called thermogenin and is predominantly found in brown adipose tissue (BAT). Here it is known to be vital for the maintenance of body temperature, especially for small mammals. As the essential component of non-shivering thermogenesis, it possesses the ability to uncouple the electrochemical gradient, generated by respiration, and dissipate the generated energy as heat.<ref>Rousset S, Alves-Guerra M-C, Mozo J, Miroux B, Cassard-Doulcier A-M, Bouillaud F, Ricquier D (2004). The biology of mitochondrial uncoupling proteins. Diabetes. 53(suppl 1):S130-S135.</ref><br />
UCP1 could be inhibited by cytosolic purine nucleotides in their di- and tri-phosphate form such as ADP, ATP, GDP and GTP. In the presence of Mg2+ cations, which can bind to the di- and tri-phosphate moieties of the purine nucleotides, this inhibitory effects is reduced.<ref>Klingenspor M, Fromme T (2012). Brown adipose tissue. In: Symonds ME, editor. Adipose tissue biology. New York, NY: Springer New York. p. 39-69.</ref> The activation of UCP1 is induced by long-chain fatty acids, which are liberated as a result of adrenergic stimulation.<ref>Fedorenko A, Lishko PV, Kirichok Y (2012). Mechanism of fatty-acid-dependent ucp1 uncoupling in brown fat mitochondria. Cell. 151(2):400-413.</ref> In detail, when norepinephrine is released by the sympathetic nervous system, it binds and stimulates the β3-adrenergic receptor of brown adipocytes, leading to the activation of adenylyl cyclase (AC) and an increase in the level of cAMP. The released messenger cAMP stimulates PKA, which phosphorylates and activates the lipases HSL as well as ATGL that subsequently degrade tri- and di-glycerides resulting in the release of free fatty acids. The long-chain, fatty acids get oxidized and activate UCP1, which thereby initiates the uncoupling of mitochondrial respiration from ATP synthesis by causing a proton leak. In the course of this, protons, which were pumped by the electron transport chain across the mitochondrial membrane, can flow back from the intermembrane space into the matrix, whereby the inner mitochondrial membrane potential is dissipated and heat generated.<ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiological Reviews. 84(1):277-359.</ref> <ref>Klingenspor M (2003). Cold-induced recruitment of brown adipose tissue thermogenesis. Experimental Physiology. 88(1):141-148.</ref> However, the exact mode of action of UCP1 has not yet been completely understood.<ref>Bertholet AM, Kirichok Y (2016). Ucp1: A transporter for h+ and fatty acid anions. Biochimie.1-7.</ref> <ref>Li Y, Fromme T, Schweizer S, Schottl T, Klingenspor M (2014). Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes. EMBO reports. 15(10):1069-1076.</ref><br />
During the first 30 years after the discovery of UCP1, it was believed that brown adipose tissue containing UCP1 can only be found in placental mammals, however, by now it was proven that the protein is also present in marsupials, fish and amphibians.<ref>Hughes DA, Jastroch M, Stoneking M, Klingenspor M (2009). Molecular evolution of ucp1 and the evolutionary history of mammalian non-shivering thermogenesis. BMC Evolutionary Biology. 9(1):4.</ref> <ref>Klingenspor M, Fromme T, Hughes Jr DA, Manzke L, Polymeropoulos E, Riemann T, Trzcionka M, Hirschberg V, Jastroch M (2008). An ancient look at ucp1. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1777(7–8):637-641.</ref> To find out whether the different types of UCP1 share common characteristics and are evolutionary related, scientists recently began focussing on studies that further investigate and compare these proteins. What has already been found out is that the murine as well as human UCP1 can be activated by fatty acids or retinoids and inhibited by purine nucleotides. However, there is also proof for interspecies differences, like the discovery that rodent UCP1 orthologs exhibit a basal proton conductance, whereas human uncoupling proteins have selectively lost the basal proton conductance.<ref>Rodríguez-Sánchez L, Rial E (2016). The distinct bioenergetic properties of the human ucp1. Biochimie.</ref><br />
<br />
== References ==</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Uncoupling_proteins&diff=135233Uncoupling proteins2017-05-05T12:49:10Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=UCP<br />
|description='''Uncoupling proteins''' (UCPs) are mitochondrial anion carrier proteins that can be found in the inner mitochondrial membranes of animals and plants. They can act as uncouplers by dissipating the proton electrochemical gradient ([[mitochondrial membrane potential]]), generated by the [[electron transfer system]] by pumping protons from the mitochondrial matrix to the mitochondrial intermembrane space.<br />
}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Uncoupler<br />
}}<br />
== Uncoupling protein homologues ==<br />
<br />
The gene family of uncoupling proteins (UCP) includes five mitochondrial solute carriers 25 (SLC25), named UCP1 (SLC25A7), UCP2 (SLC25A48), UCP3 (SLC25A9), UCP4 (SLC25A27) and UCP5 (SLC25A14).<ref>Ramsden DB, Ho PW-L, Ho JW-M, Liu HF, So DHF, Tse HM, Chan KH, Ho SL (2012). Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain and Behavior. 2(4), 468–478.</ref>. These proteins have a tripartite structure and are located in the inner membrane of mitochondria. Presumably, all of them contribute to the metabolic regulation in response to cold, including ROS and lipid metabolism, apoptosis and thermogenesis.<ref>Criscuolo F, Gonzalez‐Barroso MdM, Bouillaud F, Ricquier D, Miroux B, Sorci G (2005). Mitochondrial uncoupling proteins: New perspectives for evolutionary ecologists. The American Naturalist. 166(6):686-699.</ref> The thermogenic function of UCP1, which was the first uncoupling protein to be discovered in 1978 <ref>Nicholls DG, Bernson VSM, Heaton GM (1978). The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. In: Girardier L, Seydoux J, editors. Effectors of thermogenesis: Proceedings of a symposium held at geneva (switzerland) on 14 to 16 july 1977. Basel: Birkhäuser Basel. p. 89-93.</ref>, is already well known, whereas the exact functions of the closely related paralogues UCP2 and UCP3 are yet to be investigated. <ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiological Reviews. 84(1):277-359.</ref> <ref>Ricquier D, Bouillaud F (2000). The uncoupling protein homologues: Ucp1, ucp2, ucp3, stucp and atucp. Biochemical Journal. 345(2):161-179.</ref>. UCP4 and UCP5 are primarily expressed in the central nervous system (CNS) and were found out to function as essential uncouplers of oxidative phosphorylation and have protective function for cells by reducing oxidative stress (ROS).<br />
<br />
== Uncoupling protein 1 (UCP1) ==<br />
<br />
The uncoupling protein 1 (UCP1) is also called thermogenin and can be predominantly found in brown adipose tissue (BAT). Here it is known to be vital for the maintenance of body temperature, especially for small mammals. As the essential component of non-shivering thermogenesis, it possesses the ability to uncouple the electrochemical gradient, generated by respiration, and dissipate the generated energy as heat.<ref>Rousset S, Alves-Guerra M-C, Mozo J, Miroux B, Cassard-Doulcier A-M, Bouillaud F, Ricquier D (2004). The biology of mitochondrial uncoupling proteins. Diabetes. 53(suppl 1):S130-S135.</ref><br />
UCP1 could be inhibited by cytosolic purine nucleotides in their di- and tri-phosphate form such as ADP, ATP, GDP and GTP. In the presence of Mg2+ cations, which can bind to the di- and tri-phosphate moieties of the purine nucleotides, this inhibitory effects is reduced.<ref>Klingenspor M, Fromme T (2012). Brown adipose tissue. In: Symonds ME, editor. Adipose tissue biology. New York, NY: Springer New York. p. 39-69.</ref> The activation of UCP1 is induced by long-chain fatty acids, which are liberated as a result of adrenergic stimulation.<ref>Fedorenko A, Lishko PV, Kirichok Y (2012). Mechanism of fatty-acid-dependent ucp1 uncoupling in brown fat mitochondria. Cell. 151(2):400-413.</ref> In detail, when norepinephrine is released by the sympathetic nervous system, it binds and stimulates the β3-adrenergic receptor of brown adipocytes, leading to the activation of adenylyl cyclase (AC) and an increase in the level of cAMP. The released messenger cAMP stimulates PKA, which phosphorylates and activates the lipases HSL as well as ATGL that subsequently degrade tri- and di-glycerides resulting in the release of free fatty acids. The long-chain, fatty acids get oxidized and activate UCP1, which thereby initiates the uncoupling of mitochondrial respiration from ATP synthesis by causing a proton leak. In the course of this, protons, which were pumped by the electron transport chain across the mitochondrial membrane, can flow back from the intermembrane space into the matrix, whereby the inner mitochondrial membrane potential is dissipated and heat generated.<ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiological Reviews. 84(1):277-359.</ref> <ref>Klingenspor M (2003). Cold-induced recruitment of brown adipose tissue thermogenesis. Experimental Physiology. 88(1):141-148.</ref> However, the exact mode of action of UCP1 has not yet been completely understood.<ref>Bertholet AM, Kirichok Y (2016). Ucp1: A transporter for h+ and fatty acid anions. Biochimie.1-7.</ref> <ref>Li Y, Fromme T, Schweizer S, Schottl T, Klingenspor M (2014). Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes. EMBO reports. 15(10):1069-1076.</ref><br />
During the first 30 years after the discovery of UCP1, it was believed that brown adipose tissue containing UCP1 can only be found in placental mammals, however, by now it was proven that the protein is also present in marsupials, fish and amphibians.<ref>Hughes DA, Jastroch M, Stoneking M, Klingenspor M (2009). Molecular evolution of ucp1 and the evolutionary history of mammalian non-shivering thermogenesis. BMC Evolutionary Biology. 9(1):4.</ref> <ref>Klingenspor M, Fromme T, Hughes Jr DA, Manzke L, Polymeropoulos E, Riemann T, Trzcionka M, Hirschberg V, Jastroch M (2008). An ancient look at ucp1. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1777(7–8):637-641.</ref> To find out whether the different types of UCP1 share common characteristics and are evolutionary related, scientists recently began focussing on studies that further investigate and compare these proteins. What has already been found out is that the murine as well as human UCP1 can be activated by fatty acids or retinoids and inhibited by purine nucleotides. However, there is also proof for interspecies differences, like the discovery that rodent UCP1 orthologs exhibit a basal proton conductance, whereas human uncoupling proteins have selectively lost the basal proton conductance.<ref>Rodríguez-Sánchez L, Rial E (2016). The distinct bioenergetic properties of the human ucp1. Biochimie.</ref><br />
<br />
== References ==</div>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Uncoupling_proteins&diff=135232Uncoupling proteins2017-05-05T12:41:54Z<p>Bufe Anja: </p>
<hr />
<div>{{MitoPedia<br />
|abbr=UCP<br />
|description='''Uncoupling proteins''' (UCPs) are mitochondrial anion carrier proteins that can be found in the inner mitochondrial membranes of animals and plants. They can act as uncouplers by dissipating the proton electrochemical gradient ([[mitochondrial membrane potential]]), generated by the [[electron transfer system]] by pumping protons from the mitochondrial matrix to the mitochondrial intermembrane space.<br />
}}<br />
{{MitoPedia topics<br />
|mitopedia topic=Uncoupler<br />
}}<br />
== Uncoupling protein homologues ==<br />
<br />
The gene family of uncoupling proteins (UCP) includes five mitochondrial solute carriers 25 (SLC25), named UCP1 (SLC25A7), UCP2 (SLC25A48), UCP3 (SLC25A9), UCP4 (SLC25A27) and UCP5 (SLC25A14).<ref>Ramsden DB, Ho PW-L, Ho JW-M, Liu HF, So DHF, Tse HM, Chan KH, Ho SL (2012). Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain and Behavior. 2(4), 468–478.</ref>. These proteins have a tripartite structure and are located in the inner membrane of mitochondria. Presumably, all of them contribute to the metabolic regulation in response to cold, including ROS and lipid metabolism, apoptosis and thermogenesis.<ref>Criscuolo F, Gonzalez‐Barroso MdM, Bouillaud F, Ricquier D, Miroux B, Sorci G (2005). Mitochondrial uncoupling proteins: New perspectives for evolutionary ecologists. The American Naturalist. 166(6):686-699.</ref> The thermogenic function of UCP1, which was the first uncoupling protein to be discovered in 1978 <ref>Nicholls DG, Bernson VSM, Heaton GM (1978). The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. In: Girardier L, Seydoux J, editors. Effectors of thermogenesis: Proceedings of a symposium held at geneva (switzerland) on 14 to 16 july 1977. Basel: Birkhäuser Basel. p. 89-93.</ref>, is already well known, whereas the exact functions of the closely related paralogues UCP2 and UCP3 are yet to be investigated. <ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiological Reviews. 84(1):277-359.</ref> <ref>Ricquier D, Bouillaud F (2000). The uncoupling protein homologues: Ucp1, ucp2, ucp3, stucp and atucp. Biochemical Journal. 345(2):161-179.</ref>. UCP4 and UCP5 are primarily expressed in the central nervous system (CNS) and were found out to function as essential uncouplers of oxidative phosphorylation and have protective function for cells by reducing oxidative stress (ROS).<br />
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== Uncoupling protein 1 (UCP1) ==<br />
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The uncoupling protein 1 (UCP1) is also called thermogenin and can be predominantly found in brown adipose tissue (BAT). Here it is known to be vital for the maintenance of body temperature, especially for small mammals. As the essential component of non-shivering thermogenesis, it possesses the ability to uncouple the electrochemical gradient, generated by respiration, and dissipate the generated energy as heat.<ref>Rousset S, Alves-Guerra M-C, Mozo J, Miroux B, Cassard-Doulcier A-M, Bouillaud F, Ricquier D (2004). The biology of mitochondrial uncoupling proteins. Diabetes. 53(suppl 1):S130-S135.</ref><br />
UCP1 could be inhibited by cytosolic purine nucleotides in their di- and tri-phosphate form such as ADP, ATP, GDP and GTP. In the presence of Mg2+ cations, which can bind to the di- and tri-phosphate moieties of the purine nucleotides, this inhibitory effects is reduced.<ref>Klingenspor M, Fromme T (2012). Brown adipose tissue. In: Symonds ME, editor. Adipose tissue biology. New York, NY: Springer New York. p. 39-69.</ref> The activation of UCP1 is induced by long-chain fatty acids, which are liberated as a result of adrenergic stimulation.<ref>Fedorenko A, Lishko PV, Kirichok Y (2012). Mechanism of fatty-acid-dependent ucp1 uncoupling in brown fat mitochondria. Cell. 151(2):400-413.</ref> In detail, when norepinephrine is released by the sympathetic nervous system, it binds and stimulates the β3-adrenergic receptor of brown adipocytes, leading to the activation of adenylyl cyclase (AC) and an increase in the level of cAMP. The released messenger cAMP stimulates PKA, which phosphorylates and activates the lipases HSL as well as ATGL that subsequently degrade tri- and di-glycerides resulting in the release of free fatty acids. The long-chain, fatty acids get oxidized and activate UCP1, which thereby initiates the uncoupling of mitochondrial respiration from ATP synthesis by causing a proton leak. In the course of this, protons, which were pumped by the electron transport chain across the mitochondrial membrane, can flow back from the intermembrane space into the matrix, whereby the inner mitochondrial membrane potential is dissipated and heat generated.<ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiological Reviews. 84(1):277-359.</ref> <ref>Klingenspor M (2003). Cold-induced recruitment of brown adipose tissue thermogenesis. Experimental Physiology. 88(1):141-148.</ref> However, the exact mode of action of UCP1 has not yet been completely understood.<ref>Bertholet AM, Kirichok Y (2016). Ucp1: A transporter for h+ and fatty acid anions. Biochimie.1-7.</ref> <ref>Li Y, Fromme T, Schweizer S, Schottl T, Klingenspor M (2014). Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes. EMBO reports. 15(10):1069-1076.</ref><br />
During the first 30 years after the discovery of UCP1, it was believed that brown adipose tissue containing UCP1 can only be found in placental mammals, however, by now it was proven that the protein is also present in marsupials, fish and amphibians.<ref>Hughes DA, Jastroch M, Stoneking M, Klingenspor M (2009). Molecular evolution of ucp1 and the evolutionary history of mammalian non-shivering thermogenesis. BMC Evolutionary Biology. 9(1):4.</ref> <ref>Klingenspor M, Fromme T, Hughes Jr DA, Manzke L, Polymeropoulos E, Riemann T, Trzcionka M, Hirschberg V, Jastroch M (2008). An ancient look at ucp1. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1777(7–8):637-641.</ref> To find out whether the different types of UCP1 share common characteristics and are evolutionary related, scientists recently began focussing on studies that further investigate and compare these proteins. What has already been found out is that the murine as well as human UCP1 can be activated by fatty acids or retinoids and inhibited by purine nucleotides. However, there is also proof for interspecies differences, like the discovery that rodent UCP1 orthologs exhibit a basal proton conductance, whereas human uncoupling proteins have selectively lost the basal proton conductance.<ref>Rodríguez-Sánchez L, Rial E (2016). The distinct bioenergetic properties of the human ucp1. Biochimie.</ref></div>Bufe Anja