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10th Conference of the International Coenzyme Q10 Association, Hamburg, 2022 +
10th European Algae Industry Summit, Reykjavik, Iceland, 2020 +
10th Int. CeBiTec Research Conference, Bielefeld, Germany, 2021 +
10th International Luebeck Conference on the Pathophysiology and Pharmacology of Erythropoietin and other Hemopoietic Growth Factors +
10th International Luebeck Conference on the Pathophysiology and Pharmacology of Erythropoietin and other Hemopoietic Growth Factors, Lübeck, DE, [https://www.physio.uni-luebeck.de/index.php?id=162 10th International Luebeck Conference] +
10th Italian Meeting on Mitochondrial Diseases , Virtual, 2020 +
BIT’s 10th World Gene Convention-2019 (WGC-2019), Qingdao, China, 2019 +
115th ITC: Evolutionary mitochondrial biology: molecular, biochemical, and metabolic diversity, Titisee, Germany. +
11th Annual Congress of Cardiology, Suzhou, China, 2019 +
11th ÖGMBT Annual Meeting - Inside the world of biomolecules, Salzburg, Austria, 2019 +
MitoGlobal
12th FENS Forum of Neuroscience, Glasgow, United Kingdom, 2020 +
12th International Conference on Obesity and Eating Disorders, Vienna, Austria, 2023
== General Information ==
:::: The theme of the conference is "New Emerging Challenges in Obesity and their Prevention"
== Venue ==
:::: [https://obesity.euroscicon.com/ How to get there]
== Program ==
:::: Program available [https://obesity.euroscicon.com/program-schedule here]
== Organizers ==
:::: The list of organizers can be found [https://obesity.euroscicon.com/organizing-committee here]
== Registration ==
:::: [https://obesity.euroscicon.com/registration Registration and more information]
:::: Early registration deadline: 203-01-27
:::: Late registration deadline: 2023-04-10 +
12th ÖGMBT Annual Meeting - Biomolecules in/for 21st century, Virtual Event, 2020 '''''- Conference will be held via a virtual interactive meeting. Oroboros Instruments will be present with a virtual booth.''''' +
13th Targeting Mitochondria Congress, Berlin, 2022 +
13th ÖGMBT Annual Meeting, Virtual, 2021 +
16th Chinese Biophysics Congress - Biophysics and human health , Chengdu, China, 2018 +
16th International Conference on Mitochondrial Medicine for Neurodegenerative Diseases 2022 Stockholm SE +
ICMMND 2022: 16th International Conference on Mitochondrial Medicine for Neurodegenerative Diseases , Stockholm, 2022 +
17th Chinese Biophysics Congress, Tianjin , China, 2019 +
17th International Biochemistry of Exercise Conference, Beijing, China, 2018 +
19th Beijing Conference and Exhibition on Instrumental Analysis, Beijing, China, 2021 +
19th Chinese Biophysics congress, Anhui Province, China, 2021 +
1st Myocardial Function Symposium: “Targets in cardiometabolic disease”, Graz, Austria, 2020 +
'''1st Workshop on Mitochondrial Functional Diagnostics - PBMCs.''' Innsbruck, Austria, 2023 +
2
2014 Mitochondrial Disease Clinical Conference, Los Angeles, Ca US; [http://www.mitoaction.org/laconference 2014 Mitochondrial Disease Clinical Conference] +
2015 Spring PaduaMuscleDays: Translational Myology in Aging and Neuromuscular Disorders, Padova, IT; [http://www.pagepressjournals.org/index.php/bam/announcement/view/176 2015 Spring PaduaMuscleDays]. +
2016 Spring PaduaMuscleDays: Muscle Decline in Aging and Neuromuscular Disorders - Mechanisms and Countermeasures, Padua, IT +
2020 PaduaMuscleDays - 30 years of translational research, Vitual Event, 2020 +
24th Kalorimetrietage, Braunschweig, Germany, 2021. +
25<sup>th</sup> Krakow Conference on Endothelium, Krakow, Poland. +
28th Congress of the Polish Physiological Society, Virtual, 2021 +
2nd International Munich ROS Meeting, Munich, Germany, 2018 +
2nd Mitochondria Conference, Lisbon, Portugal, 2023. +
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'''Oroboros distributor training'''. Innsbruck, Austria; 2023 Nov 07-09. +
'''2nd Workshop on Mitochondrial Functional Diagnostics - Diagnostic database''' Innsbruck, Austria, 2023 +
3
36th annual international congress of Czech Nutrition Society, Hradec Kralove, Czech Republic, 2020 +
37th Annual Meeting of the ISHR-ES, Porto, Portugal, 2023 +
'Mitochondria, Metabolism and Energetics': [[Media:MiPNet18.14 IOC85 Mahabaleshwar.pdf|'''38th Mahabaleshwar Seminar''']], [http://www.tifr.res.in/~dbsconf/mito2014/Home.html mito2014], including '''[[MiPNet18.14 | 85th OROBOROS O2k-Workshop]]'''. +
4
46th annual congres of the International Society of Oncology and Biomarkers, Athens, Greece, 2019 +
The 4th China Symposium on Neuro-Controlled Metabolism, Hangzhou city, China, 2021 +
4th Global Chinese Symposium & The 8th Symposium for Cross-straits on Free Radical Biology and Medicine 2018 Macao CN +
4th Global Chinese Symposium & The 8th Symposium for Cross-straits, Hong Kong and Macao on Free Radical Biology and Medicine, Macao, China, 2018 +
4th edition Metabolism & Cancer, Virtual, 2021
== Program ==
:::: [https://www.metabolism-cancer.com/program/ here]
== Organizers ==
:::: The list of organizers can be found [https://www.metabolism-cancer.com/under-construction/ here]
== Registration ==
:::: [https://www.metabolism-cancer.com/registration/ Registration and more information]
== Oroboros at MetaboCancer 2021==
:::: [[Gnaiger Erich]]: Oroboros Instruments innovations - NextGen-O2k and Bioenergetics Communications, ''May 28th at 11:25''
=== Booth ===
:::: The Oroboros team is looking forward to welcome you at our Oroboros booth which will be available at this conference.
== Support ==
[[File:Template NextGen-O2k.jpg|right|350px|link=NextGen-O2k]]
[[Category:NextGen-O2k]]
:::: Supported by project NextGen-O2k which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 859770.
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5
5th Academic Symposium of Metabolic Biology Branch of Chinese Biophysical Society, Zunyi, China, 2022 +
5th International Mitochondrial Medicine Conference Mitochondrial, Online, 2021 +
5th edition Metabolism & Cancer, Nice, France, 2023
== Venue ==
:::: [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 How to get there]
== Program ==
:::: Program available [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 here]
== Organizers ==
:::: The list of organizers can be found [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 here]
== Registration ==
:::: [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 Registration and more information] +
6
6th Annual Conference of Chinese Society for Neurobiological Control of Metabolism 2024 Quanzhou CN +
6<sup>th</sup> Annual Conference of Chinese Society for Neurobiological Control of Metabolism, Quanzhou, China, 2024 +
6th Biannual Meeting on Mitochondria Apoptosis & Cancer, Prague, Czech Republic, 2019 +
6th EU-Cardioprotection WG Meeting CA16625 on mito and metabolism as targets for cardioprotection., Virtual Event, 2021 +
6th International Conference on Tumor Microenvironment and Cellular Stress: Signaling, Metabolism, Imaging and Therapeutic Targets, Chania, Crete, Greece, 2019 +
6th Research Day, Innsbruck, Austria, 2023 +
7
77th Annual Meeting of the Japanese Cancer Association at the Osaka International Convention Center and RIHGA, Osaka, Japan, 2018 +
7th European Phycological Congress, Zagreb, Croatia, 2019 +
7th Molecular Mechanisms of Axon Degeneration Meeting, Loch Lomond, Scotland, Great Britain, 2019 +
7th World Congress on Targeting Microbiota, Krakow, Poland, 2019
== Venue ==
:::: Park Inn by Radisson Krakow Hotel
:::: Ul. Monte Cassino 2 PL
:::: 30337 - Krakow - Poland
:::: [https://www.microbiota-site.com/venue.html More information]
== Organizer ==
:::: [https://www.microbiota-site.com/committee.html Information available here]
== Programme ==
:::: [https://www.microbiota-site.com/images/2019/PDF/Targeting_Microbiota_2019_Agenda_-_V7.pdf Agenda]
== Speakers ==
:::: List of speakers can be found [https://www.microbiota-site.com/microbiota-2019-speakers.html here]
== Registration ==
:::: [https://www.microbiota-site.com/registrations.html Registration and more information] +
8
8th SMRM and Mitochondria-Metabolism Network Meeting, Pune, India, 2020
== General information ==
:::: Flyer available for [https://www.mitoeagle.org/images/b/b2/8th_SMRM_and_Mitochondria-Metabolism_Network_Meeting_Poster.pdf download]
== Venue ==
:::: Indian Institute of Science Education and Research (ISER Pune)
:::: Dr. Homi Bhabha Road
:::: Pashan, Pune 411 008
:::: INDIA
::::[http://www.iiserpune.ac.in/facilities/guesthouse-cum-convention-centre Hotel and Travel]
== Programme ==
:::: [https://indico.tifr.res.in/indico/internalPage.py?pageId=12&confId=7288 here]
== Speakers ==
:::: List of speakers can be found [https://indico.tifr.res.in/indico/internalPage.py?pageId=0&confId=7288 here]
== Organizers ==
:::: The list of organizers can be found [https://indico.tifr.res.in/indico/internalPage.py?pageId=9&confId=7288 here]
== Registration ==
:::: [https://indico.tifr.res.in/indico/internalPage.py?pageId=6&confId=7288 Registration and more information] +
9
9th ÖGMBT Annual Meeting & 8th Life Science Meeting, Innsbruck, Austria +
A
46<sup>th</sup> All India Cell Biology Conference, Navi Mumbai, India, 2024 +
AlgaEurope 2018, Amsterdam, Netherlands, 2018 +
z-Scores were devised to provide a transparent but widely-applicable scoring system for participants in proficiency tests for analytical laboratories. The essential idea is to provide an appropriate scaling of the difference between a participant’s result and the ‘assigned value’ for the concentration of the analyte. Interpretation of a z-score is straightforward but some aspects need careful attention to avoid misconception. Over time several related scores have been devised to cope with a diversified range of applications. The main types of score have recently been codified in ISO 13528 (2015). +
64<sup>th</sup> Annual International Conference of the Associate of Microbiologists of India, Jhansi, India, 2023 +
'''APS Conference: Physiological Bioenergetics: Mitochondria from Bench to Bedside, Bioenergetics17'''. San Diego CA, USA; 2017 August. +
32nd APS Annual Convention, Chicago, USA, 2020 +
AVRO - Association for Research in Vision and Ophthalmology, Honolulu, Hawaii, USA, 2018 +
Joint ASMRM and J-mit Conference, Fukuoka, Japan, 2019 +
9<sup>th</sup> Conference of the Asian Society of Mitochondrial Research and Medicine and 5<sup>th</sup> Conference of Chinese Society of Mitochondrial Research and Medicine (Chinese-Mit), [http://asmrm2012.csp.escience.cn/dct/page/65540 ASMRM 2012], Bejing CN +
10<sup>th</sup> Conference of the Asian Society of Mitochondrial Research and Medicine - [http://asmrm2013.com/common_files/mess.asp ASMRM 2013], Seoul KR +
12<sup>th</sup> Conference of the Asian Society of Mitochondrial Research and Medicine - [http://www.ig.zju.edu.cn/ASMRM/EN/ ASMRM 2015], Hangzhou CN +
[[File:ASMRM2016.jpg|500px|right]]
'''13<sup>th</sup> Conference of the Asian Society of Mitochondrial Research and Medicine and the 16<sup>th</sup> Conference of the Japanese Society of Mitochondrial Research and Medicine (J-mit). The world of mitochondrial diseases: Their diversity and heterogeneity. Shinagawa JP.''' +
'''14<sup>th</sup>Conference of the Asian Society of Mitochondrial Research and Medicine'''. Xi'an, Shaanxi, China; 2017 September. +
15th Conference of the Asian Society of Mitochondrial Research and Medicine, Busan, South Korea, 2018. +
ASMRM 2020, Singapore, SG, 2021 +
ATSPB 2023, Hall in Tirol, Austria, 2023 +
Endurance exercise on a regular basis induces skeletal and cardiac muscle performance adaptation, lower mean arterial blood pressure and metabolic adaptation in a number of organs [1,2]. The latter has been shown to involve mitochondrial biogenesis. Upon injury when training intensity decreases, as well as in aging, these events tend to reverse [2,3]. The aim of the present study was to investigate whether the level of aerobic performance affects mitochondrial respiration in platelets.
Six male and female athletes were subjected to magnetic resonance imaging (MRI) of the heart and blood sampling within three days following an anterior cruciate ligament (ACL) injury. An initial follow-up was performed at the start of rehabilitation training and a late follow up at eight months following injury. The latter exams also included a maximal incremental exercise test with gas analysis. Platelets were isolated by centrifugation and mitochondrial respiration was analyzed using a substrate-uncoupler-inhibitor-protocol.
The total heart volume (THV) was significantly lower following the period of reduced exercise intensity from the time of injury to initial follow-up (p = 0.042, n = 6). There was no significant difference in THV between initial and late follow-up. The maximal ''V''<sub>O2</sub> uptake showed a trend toward increase from initial to late follow-up (p = 0.086, n = 4). There were, however, no significant differences or any discernable trends in respiratory parameters between the time points studied.
In conclusion, there was no difference in platelet mitochondrial respiration in response to alterations in exercise level in this small pilot study. +
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]]
Within a drug discovery program derived from a project for a pharmacological treatment of mitochondrial complex I deficiency, we have developed cell-permeable prodrugs of succinate (NV118) and malonate (NV161) suitable for research use in intact cells. Succinate is an intermediate of the Krebs’ cycle and acts as mitochondrial energy substrate by providing reducing equivalents to complex II (succinate dehydrogenase) of the mitochondrial oxidative phosphorylation pathway. As succinate is converted to malate by complex II, electrons are transferred down the pathway leading to proton pumping and ATP-synthesis. Succinate, as a dicarboxylic acid, is not cell-permeable and for exogenous succinate to enter cells the cell membrane requires permeabilization, using e.g. digitonin or perfringolysin. NV118 allows the researcher to deliver succinate to the cytoplasm without disrupting the plasma membrane. Malonate is a competitive inhibitor of complex II that binds to the active site of succinate dehydrogenase, thus preventing succinate from being metabolized. Like succinate, malonate is a dicarboxylic acid that does not readily permeate through the cell membrane. By using the same prodrug strategy as for NV118, the cell-permeable analogue of malonate, NV161, has been synthesized. NV118 and NV161 are rapidly metabolized, likely by the action of carboxyesterases, releasing succinate and malonate respectively.
Cell-permeable succinate and malonate were tested in a range of human cells and tissues, such as blood cells, fibroblasts, immortalized liver cells and human heart fibers either in the Oroboros O2k-FluoRespirometer (Oroboros Instruments, Innsbruck, Austria) or in the Seahorse Bioscience XFe96 Extracellular Flux Analyser (Seahorse Bioscience, North Billerica, USA). Dose-response curves for both prodrugs were obtained in human complex I inhibited platelets and primary fibroblasts.
NV118 and NV161 dose-dependently support and inhibit succinate-linked mitochondrial respiration in intact human platelets and fibroblasts. NV161 completely inhibits succinate-linked mitochondrial respiration at about ten times lower concentration as compared to malonate. Dimethyl succinate and dimethyl malonate have previously been reported to be cell-permeable, but did not show strong evidence of efficient cell penetration in this study.
We believe that NV118 and NV161 may prove valuable as scientific tools in mitochondrial research, enabling evaluation of complex II in intact cells and tissues. Analogues of both the succinate and malonate series optimized for ''in vivo'' use are simultaneously being developed.
::[http://bioblast.at/images/0/0f/Aasander_Frostner_Poster_MiP2017.pdf '''Poster link''']
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]] +
Primary mitochondrial diseases are a heterogeneous group of rare genetic disorders affecting approximately 125 persons per million. Mutations underlying these diseases give rise to biological changes (including decrease in cellular energy production and increase in reactive oxygen species), leading to organ failure, and commonly early morbidity. Mitochondrial diseases often present in early childhood and lead to the development of severe symptoms, with severe fatigue and myopathy being some of the most prevalent and debilitating clinical signs.
There are currently no cures for mitochondrial diseases, nor any approved pharmaceutical treatments for multisystemic disorders.
Current drug development in mitochondrial diseases focuses mainly on modulation of oxidative stress, regulation of the expression of genes involved in metabolic pathways, modulation of coenzymes, induction of mitochondrial biogenesis, and energy replacement.
In this short review, we present the current landscape of mitochondrial disease drug development, focusing on small molecules in clinical trials conducted by industrial sponsors. +
[[File:BEC.png|25px|link=https://doi.org/10.26124/bec:2022-0004]] https://doi.org/10.26124/bec:2022-0004
Primary mitochondrial diseases are a heterogeneous group of rare genetic disorders affecting approximately 125 persons per million. Mutations underlying these diseases give rise to biological changes (including decrease in cellular energy production and increase in reactive oxygen species), leading to organ failure, and commonly early morbidity. Mitochondrial diseases often present in early childhood and lead to the development of severe symptoms, with severe fatigue and myopathy being some of the most prevalent and debilitating clinical signs.
There are currently no cures for mitochondrial diseases, nor any approved pharmaceutical treatments for multisystemic disorders.
Current drug development in mitochondrial diseases focuses mainly on modulation of oxidative stress, regulation of the expression of genes involved in metabolic pathways, modulation of coenzymes, induction of mitochondrial biogenesis, and energy replacement.
In this short review, we present the current landscape of mitochondrial disease drug development, focusing on small molecules in clinical trials conducted by industrial sponsors.<br><br> +
[[Aasander Frostner 2022 Abstract Bioblast]]: Primary mitochondrial diseases are a heterogeneous group of rare genetic disorders affecting approximately 125 persons per million. Mutations underlying these diseases give rise to biological changes (including decrease in energy production and increase in reactive oxygen species), leading to organ failure, and commonly early morbidity. Mitochondrial diseases often present in early childhood and lead to the development of severe symptoms, with severe fatigue and myopathy being some of the most prevalent and debilitating ones.
There is currently no cure for primary mitochondrial diseases, nor any approved pharmaceutical treatments for multisystemic disorders.
Present drug development in mitochondrial diseases focuses mainly on modulation of oxidative stress, regulation of the expression of genes involved in metabolic pathways, modulation of coenzymes, induction of mitochondrial biogenesis, and energy replacement.
In this short review, we present the current landscape of mitochondrial disease drug development, focusing on small molecules in clinical trials conducted by industrial sponsor. +
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]]
Altered myocardial metabolism and cardiac inefficiency are hallmarks of the diabetic heart, and may play a central role in the pathogenesis of diabetes related cardiac dysfunction (diabetic cardiomyopathy). Although high levels of fatty acids has been demonstrated to have adverse effects in the normal heart, its effect in the obese/diabetic heart is less clear. In the present study we have examined how an acute fat-load on the heart diet-induced obese (DIO) mice (20 week on a high-fat diet) and age-matched controls (CON) will influence mitochondrial respiration.
We found reduced OXPHOS respiration in isolated mitochondrial from DIO as compared to CON hearts. By subjecting CON hearts to a high fat-load (elevated levels of fatty acids prior to mitochondrial isolation), OXPHOS respiration and RCR (respiratory coupling ratio) were reduced. These changes were not observed in mitochondria from DIO hearts, which may suggest that in diabetes, the heart undergoes adaptation to chronic exposure of elevated circulating fatty acids, which protect these hearts from the adverse effects of an acute fat-load. +
Preprints in science are nothing new. They are well established in the physical sciences, and experiments with preprints in medical sciences date back to the 1990s. When scientists imagine the future of scientific communication, preprints are inevitably an important component. The future, in this case, was slow to arrive but it is definitely here now. A preprint is a version of a scientific article that precedes its publication in a peer-reviewed journal. At one extreme, a preprint may be unedited, never peer-reviewed, or never published in a scholarly journal but simply posted on a preprint archive. The intention, however, is that by posting an article on a preprint archive, the article is freely accessible and will receive comments from the scientific community so that it can be improved before submission to a journal. +
Cancer and Metabolism conference, Cambridge, United Kingdom, 2018 +
Abcam Mitochondria Meeting 2014, London, UK; [http://www.abcam.com/index.html?pageconfig=resource&rid=16185&viapagetrap=mitochondriafeb Abcam Mitochondria Meeting 2014] +
NADPH oxidase (Nox) is emerging as one of the major sources of cellular reactive oxygen species (ROS). While controlled ROS generation by Nox is involved in the redox regulation of physiological cellular processes, excessive ROS production leads to tissue damage [1]. Nox over-reactivity has been shown to mediate the pathogenesis of tissue injury in neurodegenerative disorders [2], ischemia-reperfusion and cardiovascular disorders. Because of the short-lived nature of ROS, it is challenging to assess and monitor ROS levels in biological specimens. Thus, the development of a method to measure NADPH oxidase-derived ROS generation would be a valuable research tool to understand mechanisms relevant to neurodegeneration and tissue injury. Furthermore, this approach might be of relevance for screening of novel Nox inhibitors, which may selectively reduce disease-related Nox-mediated ROS generation without modifying ROS physiological signaling function.
By using the Oroboros Oxygraph-2k, we applied two different protocols for measuring oxygen consumption in parallel with ROS levels in freshly isolated synaptosomes. In parallel with spin trapping EPR spectroscopy, we employed this protocol to delineate the contribution of NADPH oxidase to ROS production in young female and male C57BL6 mice. The first protocol based on using a polarographic high resolution O2k sensor to measure oxygen consumption and a fluorescence-based module to monitor the rate of NADPH-mediated hydrogen peroxide production. Consistent Nox-dependent oxygen consumption was detected in synaptosomes following activation of Nox by 5 mM NADPH (3 doses). In parallel, we also employed a WPI -electrochemical sensor to determine H2O2 in the same sample. Although we didn't detect sex-dependent discrepancy in the rate of hydrogen peroxide production by Nox in isolated synaptosomes, the HRP/Amplex Red system was associated with greater oxygen consumption and higher rates of hydrogen peroxide generation, suggesting that HRP may be inducing Nox-like activity. We verified the Nox activity using spin trapping EPR spectroscopy. Our study revealed that the Oroboros Oxygraph-2k can be successfully used for assessment of Nox activity through the parallel detection of oxygen consumption and the resulting hydrogen peroxide generation. However, we have also found that HRP exhibit NADPH-dependent, oxygen-consuming, and H<sup>2</sup>O<sup>2</sup> -producing activity. Efforts are currently exerted to test other redox-sensitive dyes for the detection of ROS in the absence of HRP.
Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H<sub>2</sub>O<sub>2</sub> generation in freshly isolated synaptosomes using high-resolution respirometry combined with fluorescence or electrochemical sensory. Our results indicate that, although synaptic mitochondria exhibit substantially higher respiratory activities (8-82 folds greater than NOX oxygen consumption depending on mitochondrial respiratory state), NADPH-dependent oxygen consumption is associated with greater H<sub>2</sub>O<sub>2</sub> production (6-7 folds higher NOX-H<sub>2</sub>O<sub>2</sub>). We also show that, in terms of the consumed oxygen, while synaptic mitochondria ‘leaked’ 0.71% ± 0.12 H<sub>2</sub>O<sub>2</sub> during NAD<sup>+</sup>-linked resting, 0.21% ± 0.04 during NAD<sup>+</sup>-linked active, and 0.07% ± 0.02 during FAD<sup>+</sup>-linked active respirations, NOX converted 38% ± 13 of O<sub>2</sub> into H<sub>2</sub>O<sub>2</sub>. Our results indicate that NOX rather than mitochondria is the major source of synaptic H<sub>2</sub>O<sub>2</sub>. The present approach may assist in the identification of redox-modulating synaptic factors that underlie a variety of physiological and pathological processes in neurons. +
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]
At the request of the author, this abstract is not made available online. +
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoeagle.org/index.php/MitoEAGLE|COST Action MitoEAGLE]]
At the request of the authors, this abstract is not made available online. +
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]] +
Mitochondrial and immune dysfunctions are often implicated in the aetiology of autism spectrum disorder (ASD). Here, we studied for the first time the relationship between ASD severity measures and mitochondrial respiratory rates in freshly isolated platelets as well as the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in isolated neutrophils. We also verified the impact of hyperbaric oxygen therapy (HBOT) on mitochondrial and immune functions as well as on ASD severity measures. Blood samples were collected from three age-matched male groups (Control (Norm-N), autistic (Aut-N), and autistic + HBOT (Aut-H); N = 10 per group). Using high resolution respirometry, we found that routine basal respiration, complex I- and complex I + II-dependent oxidative phosphorylation rate were significantly impaired in Aut-N platelets. Similarly, deficits in immune response of neutrophils were evidenced through lower rates of oxygen consumption and reactive oxygen species (ROS) production by phagocytic NOX. ASD-related behavioural outcomes were found to moderately correlate with platelets' mitochondrial bioenergetic parameters as well as with NOX-mediated activity in neutrophils. HBOT was not able to improve mitochondrial dysfunctions or to counteract ASD-related behavioral deficits. Although HBOT improved one measure of the immune response; namely, NOX-mediated superoxide burst, this was not associated with significant changes in trends of recurrent infections between groups. Taken together, our data suggest that ASD-associated mitochondria and immune deficits are detectable in platelets and neutrophils. We also found no evidence that HBOT confers any significant improvement of ASD-associated physiological or behavioural phenotypes. +
Incidents of myocardial infarction and sudden cardiac arrest vary with time of the day, but the mechanism for this effect is not clear. We hypothesized that diurnal changes in the ability of cardiac mitochondria to control calcium homeostasis dictate vulnerability to cardiovascular events.
Here we investigate mitochondrial calcium dynamics, respiratory function, and reactive oxygen species (ROS) production in mouse heart during different phases of wake versus sleep periods.
We assessed time-of-the-day dependence of calcium retention capacity of isolated heart mitochondria from young male C57BL6 mice. Rhythmicity of mitochondrial-dependent oxygen consumption, ROS production and transmembrane potential in homogenates were explored using the Oroboros O2k Station equipped with a fluorescence detection module. Changes in expression of essential clock and calcium dynamics genes/proteins were also determined at sleep versus wake time points.
Our results demonstrate that cardiac mitochondria exhibit higher calcium retention capacity and higher rates of calcium uptake during sleep period. This was associated with higher expression of clock gene Bmal1, lower expression of per2, greater expression of MICU1 gene (mitochondrial calcium uptake 1), and lower expression of the mitochondrial transition pore regulator gene cyclophilin D. Protein levels of mitochondrial calcium uniporter (MCU), MICU2, and sodium/calcium exchanger (NCLX) were also higher at sleep onset relative to wake period. While complex I and II-dependent oxygen utilization and transmembrane potential of cardiac mitochondria were lower during sleep, ROS production was increased presumably due to mitochondrial calcium sequestration.
Taken together, our results indicate that retaining mitochondrial calcium in the heart during sleep dissipates membrane potential, slows respiratory activities, and increases ROS levels, which may contribute to increased vulnerability to cardiac stress during sleep-wake transition. This pronounced daily oscillations in mitochondrial functions pertaining to stress vulnerability may at least in part explain diurnal prevalence of cardiac pathologies.
Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies for this crippling orphan disease, we have performed array based and metabolic molecular analysis on patient-derived cell lines. Our results point to the conclusion that mitochondrial biogenesis and mitochondrial dysfunction in LAM cells provide a novel target for treatment. +
Researchers in the life sciences are posting their work to preprint servers at an unprecedented and increasing rate, sharing papers online before (or instead of) publication in peer-reviewed journals. Though the popularity and practical benefits of preprints are driving policy changes at journals and funding organizations, there is little bibliometric data available to measure trends in their usage. Here, we collected and analyzed data on all 37,648 preprints that were uploaded to bioRxiv.org, the largest biology-focused preprint server, in its first five years. We find that preprints on bioRxiv are being read more than ever before (1.1 million downloads in October 2018 alone) and that the rate of preprints being posted has increased to a recent high of more than 2,100 per month. We also find that two-thirds of bioRxiv preprints posted in 2016 or earlier were later published in peer-reviewed journals, and that the majority of published preprints appeared in a journal less than six months after being posted. We evaluate which journals have published the most preprints, and find that preprints with more downloads are likely to be published in journals with a higher impact factor. Lastly, we developed Rxivist.org, a website for downloading and interacting programmatically with indexed metadata on bioRxiv preprints. +
Obesity is often associated with abnormalities in cardiac morphology and function. This study tested the hypothesis that obesity-related cardiomyopathy is caused by impaired cardiac energetics. In a mouse model of high-fat diet (HFD)-induced obesity, we applied ''in vivo'' cardiac 31P magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) to investigate cardiac energy status and function, respectively. The measurements were complemented by ex vivo determination of oxygen consumption in isolated cardiac mitochondria, the expression of proteins involved in energy metabolism, and markers of oxidative stress and calcium homeostasis. We also assessed whether HFD induced myocardial lipid accumulation using ''in vivo'' 1H MRS, and if this was associated with apoptosis and fibrosis. Twenty weeks of HFD feeding resulted in early stage cardiomyopathy, as indicated by diastolic dysfunction and increased left ventricular mass, without any effects on systolic function. ''In vivo'' cardiac phosphocreatine-to-ATP ratio and ex vivo oxygen consumption in isolated cardiac mitochondria were not reduced after HFD feeding, suggesting that the diastolic dysfunction was not caused by impaired cardiac energetics. HFD feeding promoted mitochondrial adaptations for increased utilization of fatty acids, which was however not sufficient to prevent the accumulation of myocardial lipids and lipid intermediates. Myocardial lipid accumulation was associated with oxidative stress and fibrosis, but not apoptosis. Furthermore, HFD feeding strongly reduced the phosphorylation of phospholamban, a prominent regulator of cardiac calcium homeostasis and contractility. In conclusion, HFD-induced early stage cardiomyopathy in mice is associated with lipotoxicity-associated oxidative stress, fibrosis, and disturbed calcium homeostasis, rather than impaired cardiac energetics. +
Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart.
Transverse aortic constriction (TAC) was performed in non-diabetic (''db''/+) and diabetic (''db''/''db'') mice to induce pressure overload. Magnetic resonance imaging, <sup>31</sup>P magnetic resonance spectroscopy (MRS), <sup>1</sup>H MRS, and <sup>18</sup>F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. ''In vivo'' measurements were complemented with ''ex vivo'' techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status.
The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. +
[[File:BEC.png|25px|link=https://doi.org/10.26124/bec:2022-0003]] https://doi.org/10.26124/bec:2022-0003
Mitochondrial ailments are diverse and devastating. Defects in mitochondrial DNA or its products lead to a wide range of deficiencies in the mitochondrial electron transfer system and its ensuing energy transformation. Accessory proteins required for the assembly and function of the respiratory complexes are also required for healthy, coupled, and energy-transforming mitochondria. Recently, the protein nucleotide-binding protein-like (NUBPL or IND1) was identified as an iron-sulfur cluster transfer protein specifically for Complex I. Since the presence of multiple iron-sulfur clusters in Complex I is necessary for its activity, deficiency in NUBPL leads to severely dysfunctional mitochondria, with upregulated compensatory Complex II activity. Here we present a short review of the debilitating disease related to NUBPL deficiency.<br> +
[[Stiban 2022 Abstract Bioblast]]: Mitochondrial ailments are diverse and devastating. Defects in mitochondrial DNA or its products lead to wide range of deficiencies in the mitochondrial electron transfer system and its ensuing energy production. Accessory proteins required for the assembly and function of the respiratory complexes are also required for healthy, coupled, and energy-producing mitochondria. Recently, the protein nucleotide binding protein like (NUBPL or IND1) was identified as an iron-sulfur cluster transfer protein specifically for Complex I. Since the presence of multiple iron-sulfur clusters in Complex I is necessary for its activity, deficiency in NUBPL leads to severely dysfunctional mitochondria, with upregulated compensatory Complex II activity. Here we present a short review of the debilitating disease related to NUBPL deficiency. +
St. John's Wort preparations are used for the treatment of mild to moderate depression. They are usually well tolerated but can cause adverse reactions including liver toxicity in rare cases. To date, the mechanism(s) underlying the hepatotoxicity of St. John's Wort extracts are poorly investigated. We studied the hepatocellular toxicity of hypericin and hyperforin as the two main ingredients of St. John's Wort extracts in HepG2 cells and HepaRG cells and compared the effects to citalopram (a synthetic serotonin uptake inhibitor) with a special focus on mitochondrial toxicity and oxidative stress. In HepG2 cells, hypericin was membrane-toxic at 100µM and depleted ATP at 20µM. In HepaRG cells, ATP depletion started at 5µM. In comparison, hyperforin and citalopram were not toxic up to 100µM. In HepG2 cells, hypericin decreased maximal respiration starting at 2µM and mitochondrial ATP formation starting at 10µM but did not affect glycolytic ATP production. Hypericin inhibited the activity of complex I, II and IV of the electron transfer system and caused mitochondrial superoxide accumulation in cells. The protein expression of mitochondrial superoxide dismutase 2 (SOD2) and thioredoxin 2 (TRX2) and total and reduced glutathione decreased in cells exposed to hypericin. Finally, hypericin diminished the mitochondrial DNA copy number and caused cell necrosis but not apoptosis. In conclusion, hypericin, but not hyperforin or citalopram, is a mitochondrial toxicant at low micromolar concentrations. This mechanism may contribute to the hepatotoxicity occasionally observed in susceptible patients treated with St. John's Wort preparations. +
Hypoxic-ischemic events due to intrapartum complications are the second leading cause of neonatal mortality and initiate an acute brain disorder known as hypoxic-ischemic encephalopathy (HIE). In HIE, the brain undergoes primary and secondary mitochondrial energy failure phases, between there is a latent phase where partial neuronal recovery is observed. At neuronal level, the entry of calcium due to hypoxia-ischemia, activates neuronal nitric oxide synthase (nNOS) resulting in the production of nitric oxide (•NO). This leads to accumulation of reactive oxygen and nitrogen species, causing mitochondrial damage. Mitochondrial dysfunction exacerbates the injury caused by hypoxia. Pharmacological treatments targeting mitochondria or inhibiting •NO production plays a key role in improving mitochondrial function, consequently, neuroprotection. 2-iminobiotin (2IB) inhibits nNOS and is currently in study as a neuroprotective agent.
The aim of this study is to investigate the effect of hypoxia on the developing brain in a neonatal piglet model and the pharmacological neuroprotection provided by 2IB as a modulator of neuronal •NO production.
For this purpose, a 24-48-hour-old newborn piglet (''Sus scrofa domestica'') model is used. The animals are anesthetized and placed on mechanical ventilatory support with FiO2 of 0.21 (normoxia). Throughout the experiment, they are continuously monitored using pulse oximetry and regional cerebral near-infrared spectroscopy (NIRS), invasive blood pressure measurement, integrated amplitude electroencephalogram (aEEG), central temperature, and serial blood gasses analysis. Hypoxia is induced by obstructing the endotracheal tube for 4 minutes, repeating this procedure 3 times every 30 minutes. Between each hypoxia, re ventilation with FiO2. 0.21 The administration of 2IB is done immediately after hypoxia (intravenous 0.2 mg/kg of 2IB). After 4 hours, the animal is sacrificed. Brain biopsies are taken to measure mitochondrial function. Mitochondrial respiration is measured in brain biopsies using an Oroboros Oxygraph at 37°C.
At present, this project is under development. Some experimental procedures have been already done. During hypoxia it was observed hemodynamic affectation shown by bradycardia, increased blood pressure, and decreased oxygen saturation and regional cerebral oxygen saturation, recovering between each hypoxia. On the aEEG, a voltage decrease is observed during hypoxia with subsequent recovery. In blood gasses analysis it is observed a sustained increase in lactate without recovery between hypoxia. Regarding mitochondrial function, a decrease in all respiratory indices was observed in the hypoxia group compared to the control group. We observe significant differences on maximum respiration, reserve capacity and non-mitochondrial consumption. Until now we do not have 2IB results.
The distribution and redox state of ubiquinone in rat and human tissues have been investigated. A rapid extraction procedure and direct injection onto HPLC were employed. It was found in model experiments that in postmortem tissue neither oxidation nor reduction of ubiquinone occurs. In rat the highest concentrations of ubiquinone-9 were found in the heart, kidney, and liver (130-200 micrograms/g). In brain, spleen, and intestine one-third and in other tissues 10-20% of the total ubiquinone contained 10 isoprene units. In human tissues ubiquinone-10 was also present at highest concentrations in heart, kidney, and liver (60-110 micrograms/g), and in all tissues 2-5% of the total ubiquinone contained 9 isoprene units. High levels of reduction, 70-100%, could be observed in human tissues, with the exception of brain and lung. The extent of reduction displayed a similar pattern in rat, but was generally lower. +
In the context of skeletal muscle, IL-6 plays a major role in muscle quality. The goal of this project was to study the influence of systemic IL-6 on skeletal muscle mitochondrial physiology, most notably mitochondrial function (respiration and ROS production) and mitochondrial content.
To determine the influence of interleukin-6 (IL-6) on skeletal muscle mitochondria, high-resolution respirometry was performed to simultaneously measure oxygen consumption (JO2) and ROS production in differentiated myotubes incubated with increasing IL-6 (0, 10, 50, 100 ng/mL) for 18 hours in serum free conditions. To evaluate the impact of IL-6 on mitochondrial content we performed western blots on cell lysates from treated cells, measuring proteins of the mitochondrial electron transport chain (ETC) using a cocktail antibody and PGC-1α/PGC-1ß for mitochondrial biogenesis. To determine the role of mitochondrial ROS production on JO2 and mitochondrial content, we co-treated differentiated myotubes for 18 hours with 50 and 100ng/mL IL-6 and the mitochondrial specific antioxidant, MitoQ and performed respirometry for mitochondrial functional measurements and western blots for mitochondrial content.Statistical significance was evaluated by using a 2-tailed Student’s t-test and two-way ANOVA. Post hoc all-group analyses were conducted to determine which groups were different when the model was significant.
Mitochondrial functional measurements show increased JO2 and increased ROS production in an IL-6 dose-dependent manner. Targeting mitochondrial ROS production with 0.5µm MitoQ attenuated IL-6 induced increases in JO2 and ROS production. Complexes I and II (CI, CII) of the ETC increased significantly in an IL-6 dose-wise fashion, and co-treatment with MitoQ normalized increases at 100ng/mL Il-6. 100ng/mL IL-6 significantly increased protein expression of PGC-1α and PGC-1ß. Co-treatment with MitoQ normalized IL-6 induced increase in PGC-1α.
Our data suggest that when treated chronically at a high dose, IL-6 increases mitochondrial respiration, ROS production, and content. Targeting mitochondrial ROS production normalizes these mitochondrial adaptations. The present study provides new insights into mitochondrial physiology in the context of inflammation. Therapeutically targeting mitochondrial ROS production may impact skeletal muscle quality in certain populations.
Interleukin-6 (IL-6) is a pleiotropic cytokine that has been shown to be produced acutely by skeletal muscle in response to exercise, yet chronically elevated with obesity and aging. The mechanisms by which IL-6 influences skeletal muscle mitochondria acutely and chronically are unclear. To better understand the influence of extramyocellular IL-6 on skeletal muscle mitochondrial physiology, we treated differentiated myotubes with exogenous IL-6 to evaluate the dose- and duration-dependent effects of IL-6 on salient aspects of mitochondrial biology and the role of canonical IL-6 signaling in muscle cells. Acute exposure of myotubes to IL-6 increased the mitochondrial reactive oxygen species (mtROS) production and oxygen consumption rates (JO<sub>2</sub>) in a manner that was dependent on activation of the JAK/STAT pathway. Furthermore, STAT3 activation by IL-6 was partly attenuated by MitoQ, a mitochondrial-targeted antioxidant, suggesting that mtROS potentiates STAT3 signaling in skeletal muscle in response to IL-6 exposure. In concert with effects on mitochondrial physiology, acute IL-6 exposure induced several mitochondrial adaptations, consistent with the stress-induced mitochondrial hyperfusion. Exposure of myotubes to chronically elevated IL-6 further increased mtROS with eventual loss of respiratory capacity. These data provide new evidence supporting the interplay between cytokine signaling and mitochondrial physiology in skeletal muscle. +
Hydrogen sulfide (H2S) is the third gasotransmitter described in mammals. These gasotransmitters (H2S, CO, and NO) are small molecules able to diffuse freely across membranes and thus susceptible to reach easily intracellular targets, one of which is the respiratory enzyme cytochrome oxidase subject to complete inhibition by low micromolar concentrations of these gases. However in contrast to NO or CO, H2S can be metabolized by a sulfide quinone reductase feeding the mitochondrial respiratory chain with the hydrogen atoms of sulfide. Sulfide is thus a two-sided molecule: substrate or poison according to the concentration. The aim of this chapter is to present a mean to monitor sulfide oxidation by isolated mitochondria or cells and to summarize how the properties of this amazing couple (mitochondria and sulfide) translate into practical and conceptual consequences. +
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