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MitoEAGLE blood cells 1

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COST Action CA15203 (2016-2021): MitoEAGLE
Evolution-Age-Gender-Lifestyle-Environment: mitochondrial fitness mapping


MitoEAGLE blood cells 1


Publications in the MiPMap
Åsander Frostner Eleonor*, Aburel Oana M*, Avram Vlad F*, Calabria Elisa, Castelo Rueda Maria Paulina*, Chamkha Imen*, Čižmárová Beata, Danila Maria-Daniela*, Doerrier Carolina*, Eckert Gunter P*, Ehinger Johannes K, Elmer Eskil*, Garcia-Souza Luiz F*, Gnaiger Erich*, Hoppel Florian*, Karabatsiakis Alexander*, Keppner Gloria, Kidere Dita*, Krako Jakovljević Nina, Labieniec-Watala Magdalena*, Lelcu Theia*, Micankova Petra, Michalak Slawomir*, Molina Anthony JA*, Pavlovic Kasja, Pichler Irene*, Piel Sarah, Rousar Tomas, Rybacka-Mossakowska Joanna, Schartner Melanie, Siewiera Karolina*, Silaidos Carmina*, Sjövall Fredrik*, Sobotka Ondrej*, Sumbalova Zuzana*, Swiniuch Daria, Vernerova Andrea*, Volani Chiara*, Vujacic-Mirski Ksenija*, Watala Cezary* (2020) Interlaboratory guide to mitochondrial respiratory studies with peripheral blood mononuclear cells and platelets. - Updated: 2020-03-06 - *Confirmed

» MitoEAGLE blood cells group (WG 4)

Aasander Frostner Eleonor, Aburel Oana M, Avram Vlad F, Calabria Elisa, Castelo Rueda Maria Paulina, Chamkha Imen, Cizmarova Beata, Danila Maria-Daniela, Doerrier Carolina, Eckert Gunter P, Ehinger Johannes K, Elmer Eskil, Garcia-Souza Luiz F, Gnaiger Erich, Hoppel Florian, Karabatsiakis Alexander, Keppner Gloria, Kidere Dita, Krako Jakovljevic Nina, Labieniec-Watala Magdalena, Lelcu Theia, Micankova Petra, Michalak Slawomir, Molina Anthony JA, Pavlovic Kasja, Pichler Irene, Piel Sarah, Rousar Tomas, Rybacka-Mossakowska Joanna, Schartner Melanie, Siewiera Karolina, Silaidos Carmina, Sjoevall Fredrik, Sobotka Ondrej, Sumbalova Zuzana, Swiniuch Daria, Vernerova Andrea, Volani Chiara, Vujacic-Mirski Ksenija, Watala Cezary (2020) MitoEAGLE

Abstract:

Fig. 1. Workflow in the pre-analytical and analytical phases of blood cell preparation and respiration in living cells (ce) and permeabilized cells (pce).

Contents

1. Introduction

2. Methods: respiration with living and permeabilized cells

3. Workflow: pre-analytical and analytical preparatory phase

3.1. Pre-analytical exclusion criteria

3.2. Blood sampling

3.3. Blood transport and storage

3.4. Exclusion criteria derived from haematology of whole blood and plasma

3.5. Isolation of blood cells

3.6. Storage of isolated cells

3.7. Cell count, volume, purity and viability

4. Case studies on respiration in PBMC and PLT

4.1 Effect of incubation media and cell concentration on mitochondrial respiration

4.2. Effect of sex and age on blood cell respiration

4.3 Normalization of cell and mitochondrial respiration

5. Conclusions


Version beta 01
  1. Evaluation of mitochondrial function is a potentially important diagnostic tool applicable in a wide spectrum of human pathologies. Peripheral blood provides an easily accessible source of primary human cells. However, mitochondrial respiratory studies in blood cells require improved standardization. The procedures applied in bioenergetic assessments involve multiple steps in the pre-analytical, analytical and data analysis phase. The aim of the present report is to summarize methods for preparing peripheral blood mononuclear cells (PBMC) and platelets (PLT) for application in mitochondrial respiratory studies. For this purpose we report original data from several laboratories and discuss some relevant data from the literature.
  2. The present report does not present results on patients, but is aimed at a characterization of healthy control groups. Exclusion criteria in the pre-analytical phase are related to smoking, alcohol intake, BMI, lifestyle interventions, and medications. In pathophysiological studies, subjects have to be matched with controls for sex, age and genetic background.
  3. Time of sampling, fasting and resting state require standardization. Anticoagulants are used for whole blood sampling (e.g., K-EDTA, lithium heparin, sodium citrate). Protocols are optimized on the basis of yield, cell fraction purity, intactness of plasma membrane barrier function, and respiratory results.
  4. Duration and temperature during transport and storage of whole blood has to be monitored carefully and evaluated in terms of final outcome.
  5. Characterization of whole blood provides rigorous exclusion criteria for the study of healthy control groups.
  6. Separation procedures depend on the type of cells harvested for respirometric studies (PLT, PBMC, or both). Media, centrifugation conditions, cell counting and cell viability methods are evaluated. Results on purity of preparations (e.g., PLT contamination in PBMC fraction, purity of PLT fraction), recovery and yield of cells are compared in a variety of cell separation methods and evaluated by comparative respiratory studies.
  7. Storage conditions and processing of isolated cells exert direct effects on cell respiration. Temperature, media, antibiotics, proteinase inhibitors cocktail, density of cells during storage, tilting of cell fraction might significantly affect the measurements.
  8. Specific protocols are used for respiration assessments in living and permeabilized. The type of medium used for respirometry (MiR05, RPMI, plasma) needs further evaluation.
  9. Normalization is important to interpret and compare the results of respiratory studies. It should include data on contamination of PBMC with PLT, cell viability (e.g., succinate test), flux control ratios, total protein concentration, citrate synthase activity. Some other markers, like clusters of differentiation specific for leukocytes and platelets can be taken into consideration.
  10. Finally, we summarize emerging recommendations for mitochondrial respiratory studies in living and permeabilized PBMC and PLT towards building a data base of healthy subjects that can be used as controls in clinical studies.

Work in progress

MitoEAGLE WG4 Innsbruck AT
  1. To summarize in a first section the respirometric tests applied for functional evaluation of methods presented in steps 2 to 7.
  2. The methods applied in each of the steps 2 to 7 will be introduced and compared, and directly evaluated by presenting and discussing the respirometric results obtained with different preparation methods.
  3. Cell purity and intactness of the plasma membrane barrier function (the term cell viability is avoided) represent important outcomes independent of respiration, to compare and evaluate the different methods in steps 2 to 7.
  4. A short final summary will be presented on respirometric case studies (steps 8-10).
  5. We aim at presenting summary figures and tables with reference to original publications.
  6. Summary figures and tables including unpublished data are included, if the data are made available (Supplement or accessible database). Raw data should be saved on your server, then collected on a server of the corresponding author, with a statement in our manuscript that raw data are available upon request from the corresponding author (DatLab files and Excel spreadsheets).
  • We suggest to use the abbrevitions PBMC and PLT irrespective of singular or plural. In contrast, when using the full word, it is perfectly OK to say 'platelet respiration' or 'respiration of platelets', similarly 'platelet cell count' or 'cell count of platelets'.
  • The term 'cell viability' should be defined strictly on the basis of measurement of plasma membrane permeability, providing an explanation of the method applied. Living cells, ce, are populations of cells that consist predominantly of viable cells, vce, but may contain a small fraction of dead cells, dce. ROUTINE respiration can be measured only in living cells, whereas determination of OXPHOS capacity requires selective permeabilization of the plasma membrane to support mitochondrial respiration in permeabilized cells, pce, by saturating [ADP] and [Pi] ( Gnaiger et al 2019 ). Cell viability must be distinguished from cell activation state, and if the terms appears to be ambiguous, it should be avoided and the meaning should be communicated in terms of the methods applied to assess the state of a living cell population.


Manuscript table and figure blocks

  • Section: Workflow # and Title
  • Summary: Aims [1] and recommendations
  • Specify study group [2], consider sensitive data
  • Methods
  • Describe results shown in table and figure, as median and inter-quartile range; provide text with full information
  • Discussion
  • Conclusions, provide full information
  • References
(1) Define the aim, the question:
  • Scientific: focus on accuracy of best physiological data, separate isolation proocols for PBMC and PLT, if necessary.
  • Diagnostic: discriminative tool relying on reproducibility, practicability and minimum available blood volume; if necessary, accept compromises when PBMC and PLT should be analyzed from the same blood sample.
(2) Include patient data solely for messages on methods (comparison of the effect of anticoagulants, ..); patient data can be reduced to showing fractional effects of methodological variations.
Fig. 2. Dataflow from cohort design to respirometric SUIT protocols and technical repeats. For the meaning of numbers in circles, see Figure 1.


Templates for PBMC and PLT data base

  • 2018-12-18 An updated template for the PBMC and PLT data base is in preparation (Luiz, Caro, Erich).
    • Luiz will be responsible for collecting and merging the data sheets based on previous templates, summarizing all data in the new template.
    • This will be the basis of the WG4 Task Group meeting in March 2019. We have to fix the dates.
» MitoEAGLE template PLT final.xlsx
» MitoEAGLE template PBMC final.xlsx
  • We will collect and analyze all data, in preparation of a database for Open Access in conjunction with the journal publication.


References

MitoEAGLE blood cells reviews

 YearReferenceOrganismTissue;cellDiseases
MiPNet21.17 BloodCellsIsolation2020-10-22
O2k-Protocols
O2k-Protocols: Isolation of blood cells for HRR.
HumanBlood cells
Platelet
Alfatni 2020 J Clin Med2020Alfatni A, Riou M, Charles AL, Meyer A, Barnig C, Andres E, Lejay A, Talha S, Geny B (2020) Peripheral blood mononuclear cells and platelets mitochondrial dysfunction, oxidative stress, and circulating mtDNA in cardiovascular diseases. J Clin Med 9 pii:E311.HumanBlood cells
Platelet
Cardiovascular
Petrus 2019 Physiol Res2019Petrus AT, Lighezan DL, Dănilă MD, Duicu OM, Sturza A, Muntean DM, Ionită I (2019) Assessment of platelet respiration as emerging biomarker of disease. Physiol Res 68:347-63.HumanPlatelet
Blood cells
Braganza 2019 Mol Aspects Med2019Braganza A, Annarapu GK, Shiva S (2019) Blood-based bioenergetics: An emerging translational and clinical tool. Mol Aspects Med 2019:100835.HumanBlood cells
Platelet
Hsiao 2018 Anal Biochem2018Hsiao CP, Hoppel C (2018) Analyzing mitochondrial function in human peripheral blood mononuclear cells. Anal Biochem 549:12-20.HumanBlood cells
Ost 2018 Curr Opin Clin Nutr Metab Care2018Ost M, Doerrier C, Gama-Perez P, Moreno-Gomez S (2018) Analysis of mitochondrial respiratory function in tissue biopsies and blood cells. Curr Opin Clin Nutr Metab Care 21:336-42.Blood cells
Platelet
Skeletal muscle
Liver
Fat
Doerrier 2018 Methods Mol Biol2018Doerrier C, Garcia-Souza LF, Krumschnabel G, Wohlfarter Y, Mészáros AT, Gnaiger E (2018) High-Resolution FluoRespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle, and isolated mitochondria. Methods Mol Biol 1782:31-70. https://doi.org/10.1007/978-1-4939-7831-1_3Human
Mouse
Rat
Saccharomyces cerevisiae
Heart
Skeletal muscle
Endothelial;epithelial;mesothelial cell
Blood cells
HEK
Platelet
Sumbalova 2018 Nova Sciences2018Sumbalová Z, Garcia-Souza LF, Cizmarova B, Volani C, Gnaiger E (2018) Analysis of mitochondrial function in human blood cells. In: Recent advances in mitochondrial medicine and coenzyme Q10. Gvozdjáková A, Cornelissen G, Singh RB eds, Nova Sciences:255-68.HumanBlood cells
Zhang 2018 Mil Med Res2018Zhang H, Feng YW, Yao YM (2018) Potential therapy strategy: targeting mitochondrial dysfunction in sepsis. Mil Med Res 5:41. https://doi.org/10.1186/s40779-018-0187-0Platelet
Blood cells
Sepsis
Westerlund 2017 Pediatr Res2017Westerlund E, Marelsson SE, Ehinger JK, Sjövall F, Morota S, Åsander Frostner E, Oldfors A, Darin N, Lundgren J, Hansson MJ, Fellman V, Elmér E (2017) Oxygen consumption in platelets as an adjunct diagnostic method for pediatric mitochondrial disease. Pediatr Res 83:455-65.HumanPlatelet
Blood cells
Tyrrell 2016 Redox Biol2016Tyrrell DJ, Bharadwaj MS, Jorgensen MJ, Register TC, Molina AJ (2016) Blood cell respirometry is associated with skeletal and cardiac muscle bioenergetics: Implications for a minimally invasive biomarker of mitochondrial health. Redox Biol 10:65-77. https://doi.org/10.1016/j.redox.2016.09.009Other mammals
Human
Skeletal muscle
Blood cells
Platelet
Kramer 2014 Redox Biol2014Kramer PA, Ravi S, Chacko B, Johnson MS, Darley-Usmar VM (2014) A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: implications for their use as bioenergetic biomarkers. Redox Biol 2:206–10.HumanBlood cells
Platelet
Van Bergen 2014 Mitochondrion2014Van Bergen NJ, Blake RE, Crowston JG, Trounce IA (2014) Oxidative phosphorylation measurement in cell lines and tissues. Mitochondrion 15:24-33.Human
Mouse
Nervous system
Blood cells

MitoEAGLE blood cells data

 YearReferenceOrganismTissue;cellDiseases
Janowska 2020 Toxicol In Vitro2020Janowska JI, Piel S, Saliba N, Kim CD, Jang DH, Karlsson M, Kilbaugh TJ, Ehinger JK (2020) Mitochondrial respiratory chain Complex I dysfunction induced by N-methyl carbamate ex vivo can be alleviated with a cell-permeable succinate prodrug carbamate toxicity and treatment. Toxicol In Vitro 65:104794.HumanPlatelet
Blood cells
Kline 2020 Nitric Oxide2020Kline JA, Puskarich MA, Pike JW, Zagorski J, Alves NJ (2020) Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism. Nitric Oxide 96:20-8.HumanPlatelet
Blood cells
Other
Gvozdjakova 2019 Bratisl Lek Listy2019Gvozdjakova A, Sumbalova Z, Kucharska J, Chladekova A, Rausova Z, Vancova O, Komlosi M, Ulicna O, Mojto V (2019) Platelet mitochondrial bioenergetic analysis in patients with nephropathies and non-communicable diseases: a new method. Bratisl Lek Listy 120:630-35.HumanPlatelet
Blood cells
Other
Rose 2019 Am J Physiol Endocrinol Metab2019Rose S, Carvalho E, Diaz EC, Cotter M, Bennuri SC, Azhar G, Frye RE, Adams SH, Børsheim E (2019) A comparative study of mitochondrial respiration in circulating blood cells and skeletal muscle fibers in women. Am J Physiol Endocrinol Metab 317:E503-E512. https://doi.org/10.1152/ajpendo.00084.2019HumanSkeletal muscle
Blood cells
Platelet
Zverova 2019 Neuropsychiatr Dis Treat2019Zvěřová M, Hroudová J, Fišar Z, Hansíková H, Kališová L, Kitzlerová E, Lambertová A, Raboch J (2019) Disturbances of mitochondrial parameters to distinguish patients with depressive episode of bipolar disorder and major depressive disorder. Neuropsychiatr Dis Treat 15:233-40.HumanPlatelet
Blood cells
Other
Braganza 2019 JCI Insight2019Braganza A, Corey CG, Santanasto AJ, Distefano G, Coen PM, Glynn NW, Nouraie SM, Goodpaster BH, Newman AB, Shiva S (2019) Platelet bioenergetics correlate with muscle energetics and are altered in older adults. JCI Insight 5:128248.HumanSkeletal muscle
Blood cells
Platelet
Aging;senescence
Fisar 2019 Clin Biochem2019Fišar Z, Jirák R, Zvěřová M, Setnička V, Habartová L, Hroudová J, Vaníčková Z, Raboch J (2019) Plasma amyloid beta levels and platelet mitochondrial respiration in patients with Alzheimer's disease. Clin Biochem 72:71-80.HumanPlatelet
Blood cells
Alzheimer's
Kulkarni 2019 Haematologica2019Kulkarni PP, Tiwari A, Singh N, Gautam D, Sonkar VK, Agarwal V, Dash D (2019) Aerobic glycolysis fuels platelet activation: small-molecule modulators of platelet metabolism as anti-thrombotic agents. Haematologica 104:806-18.HumanBlood cells
Platelet
Cancer
Hsu 2019 J Clin Med2019Hsu CC, Tsai HH, Fu TC, Wang JS (2019) Exercise training enhances platelet mitochondrial bioenergetics in stroke patients: a randomized controlled trial. J Clin Med 8:E2186.HumanPlatelet
Blood cells
Cardiovascular
Gautam 2019 Sci Rep2019Gautam D, Tiwari A, Nath Chaurasia R, Dash D (2019) Glutamate induces synthesis of thrombogenic peptides and extracellular vesicle release from human platelets. Sci Rep 9:8346.HumanPlatelet
Blood cells
Sowton 2018 Biochem Biophys Res Commun2018Sowton AP, Millington-Burgess SL, Murray AJ, Harper MT (2018) Rapid kinetics of changes in oxygen consumption rate in thrombin-stimulated platelets measured by high-resolution respirometry. Biochem Biophys Res Commun 503:2721-27.HumanPlatelet
Blood cells
Silaidos 2018 Biol Sex Differ2018Silaidos C, Pilatus U, Grewal R, Matura S, Lienerth B, Pantel J, Eckert GP (2018) Sex-associated differences in mitochondrial function in human peripheral blood mononuclear cells (PBMCs) and brain. Biol Sex Differ 9:34.HumanNervous system
Blood cells
Alzheimer's
Baaten 2018 Haematologica2018Baaten CCFMJ, Moenen FCJI, Henskens YMC, Swieringa F, Wetzels RJH, van Oerle R, Heijnen HFG, Ten Cate H, Holloway GP, Beckers EAM, Heemskerk JWM, van der Meijden PEJ (2018) Impaired mitochondrial activity explains platelet dysfunction in thrombocytopenic cancer patients undergoing chemotherapy. Haematologica 103:1557-67.HumanBlood cells
Platelet
Cancer
Gatterer 2018 J Sports Sci Med2018Gatterer H, Menz V, Salazar-Martinez E, Sumbalova Z, Garcia-Souza LF, Cizmarova B, Gnaiger E, Burtscher M (2018) Exercise performance, muscle oxygen extraction and blood cell mitochondrial respiration after repeated-sprint and sprint interval training in hypoxia: a pilot study. J Sports Sci Med 17:339-347.HumanBlood cells
Platelet
Durand 2018 Blood Purif2018Durand PY, Nicco C, Serteyn D, Attaf D, Edeas M (2018) Microbiota quality and mitochondrial activity link with occurrence of muscle cramps in hemodialysis patients using citrate dialysate: a pilot study. Blood Purif 46:301-8.HumanPlatelet
Blood cells
Jang 2018 J Med Toxicol2018Jang DH, Khatri UG, Mudan A, Love JS, Owiredu S, Eckmann DM (2018) Translational application of measuring mitochondrial functions in blood cells obtained from patients with acute poisoning. J Med Toxicol 14:144-51.HumanBlood cellsCardiovascular
Chou 2018 Int J Cardiol2018Chou CH, Fu TC, Tsai HH, Hsu CC, Wang CH, Wang JS (2018) High-intensity interval training enhances mitochondrial bioenergetics of platelets in patients with heart failure. Int J Cardiol 274:214-20.HumanPlatelet
Blood cells
Cardiovascular
Clere-Jehl 2018 Shock2018Clere-Jehl R, Helms J, Kassem M, Le Borgne P, Delabranche X, Charles AL, Geny B, Meziani F, Bilbault P (2018) Septic shock alters mitochondrial respiration of lymphoid cell-lines and human peripheral blood mononuclear cells: the role of plasma. Shock 51:97-104.HumanBlood cellsSepsis
Doucet 2018 Mol Pharmacol2018Doucet MS, Jougleux JL, Poirier SJ, Cormier M, Leger JL, Surette ME, Pichaud N, Touaibia M, Boudreau LH (2018) Identification of peracetylated quercetin as a selective 12-lipoxygenase pathway inhibitor in human platelets. Mol Pharmacol 95:139-50.HumanPlatelet
Blood cells
Boeck 2018 Sci Rep2018Boeck C, Salinas-Manrique J, Calzia E, Radermacher P, von Arnim CAF, Dietrich DE, Kolassa IT, Karabatsiakis A (2018) Targeting the association between telomere length and immunocellular bioenergetics in female patients with Major Depressive Disorder. Sci Rep 8:9419.HumanBlood cellsNeurodegenerative
Piel 2018 Intensive Care Med Exp2018Piel S, Ehinger JK, Chamkha I, Frostner EÅ, Sjövall F, Elmér E, Hansson MJ (2018) Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production. Intensive Care Med Exp 6:22.HumanPlatelet
Blood cells
Hedges 2018 J Appl Physiol (1985)2018Hedges CP, Woodhead JST, Wang HW, Mitchell CJ, Cameron-Smith D, Hickey AJR, Merry TL (2018) Peripheral blood mononuclear cells do not reflect skeletal muscle mitochondrial function or adaptation to high-intensity interval training in healthy young men. J Appl Physiol (1985) 126:454-61.HumanSkeletal muscle
Blood cells
Michalak 2017 Oxid Med Cell Longev2017Michalak S, Florczak-Wyspiańska J, Rybacka-Mossakowska J, Ambrosius W, Osztynowicz K, Baszczuk A, Kozubski W, Wysocka E (2017) Mitochondrial respiration in intact peripheral blood mononuclear cells and sirtuin 3 activity in patients with movement disorders. Oxid Med Cell Longev 2017:9703574.Blood cellsOther
Rezania 2017 Thromb Res2017Rezania S, Puskarich MA, Petrusca DN, Neto-Neves EM, Rondina MT, Kline JA (2017) Platelet hyperactivation, apoptosis and hypercoagulability in patients with acute pulmonary embolism. Thromb Res 155:106-15.HumanBlood cells
Platelet
Cardiovascular
Other
Wu 2017 Sci Rep2017Wu LH, Chang SC, Fu TC, Huang CH, Wang JS (2017) High-intensity interval training improves mitochondrial function and suppresses thrombin generation in platelets undergoing hypoxic stress. Sci Rep 7:4191.HumanBlood cells
Platelet
Jang 2017 Mitochondrion2017Jang DH, Greenwood JC, Owiredu S, Ranganathan A, Eckmann DM (2017) Mitochondrial networking in human blood cells with application in acute care illnesses. Mitochondrion 44:27-34.HumanBlood cells
Bynum 2016 Transfusion2016Bynum JA, Adam Meledeo M, Getz TM, Rodriguez AC, Aden JK, Cap AP, Pidcoke HF (2016) Bioenergetic profiling of platelet mitochondria during storage: 4°C storage extends platelet mitochondrial function and viability. Transfusion 56 Suppl 1:S76-84.HumanBlood cells
Platelet
Watala 2016 Int J Pharm2016Watala C, Karolczak K, Kassassir H, Siewiera K, Maczynska K, Pieniazek A, Labieniec-Watala M (2016) How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Platelet membrane zeta potential and other membrane-associated phenomena. Int J Pharm 500:379-89.HumanBlood cells
Platelet
Chakraborty 2016 Pancreatology2016Chakraborty M, Hickey AJ, Petrov MS, Macdonald JR, Thompson N, Newby L, Sim D, Windsor JA, Phillips AR (2016) Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute pancreatitis. Pancreatology 16:739-47.Human
Rat
Blood cellsOther
Ehinger 2016 Nat Commun2016Ehinger JK, Piel S, Ford R, Karlsson M, Sjövall F, Frostner EÅ, Morota S, Taylor RW, Turnbull DM, Cornell C, Moss SJ, Metzsch C, Hansson MJ, Fliri H, Elmér E (2016) Cell-permeable succinate prodrugs bypass mitochondrial Complex I deficiency. Nat Commun 7:12317. https://doi.org/10.1038/ncomms12317Heart
Blood cells
Fibroblast
Inherited
Boeck 2016 Mitochondrion2016Boeck C, Koenig AM, Schury K, Geiger ML, Karabatsiakis A, Wilker S, Waller C, Gündel H, Fegert JM, Calzia E, Kolassa IT (2016) Inflammation in adult women with a history of child maltreatment: The involvement of mitochondrial alterations and oxidative stress. Mitochondrion 30:197-207.HumanBlood cells
Lymphocyte
Neurodegenerative
Fisar 2016 Curr Alzheimer Res2016Fišar Z, Hroudová J, Hansíková H, Spáčilová J, Lelková P, Wenchich L, Jirák R, Zvěřová M, Zeman J, Martásek P, Raboch J (2016) Mitochondrial respiration in the platelets of patients with Alzheimer's disease. Curr Alzheimer Res 13:930-41.HumanBlood cells
Platelet
Alzheimer's
Jang 2016 Clin Toxicol (Phila)2016Jang DH, Shofer FS, Weiss SL, Becker LB (2016) Impairment of mitochondrial respiration following ex vivo cyanide exposure in peripheral blood mononuclear cells. Clin Toxicol (Phila) 54:303-7.HumanBlood cells
Lymphocyte
Ehinger 2016 Mov Disord2016Ehinger JK, Morota S, Hansson MJ, Gesine P, Elmér E (2016) Mitochondrial respiratory function in peripheral blood cells from Huntington’s disease patients. Mov Disord doi:10.1002/mdc3.12308.HumanBlood cells
Lymphocyte
Platelet
Neurodegenerative
Tsai 2016 Sci Rep2016Tsai HH, Chang SC, Chou CH, Weng TP, Hsu CC, Wang JS (2016) Exercise training alleviates hypoxia-induced mitochondrial dysfunction in the lymphocytes of sedentary males. Sci Rep 6:35170.HumanLymphocyte
Blood cells
Vevera 2016 Physiol Res2016Vevera J, Fišar Z, Nekovářová T, Vrablík M, Zlatohlávek L, Hroudová J, Singh N, Raboch J, Valeš K (2016) Statin-induced changes in mitochondrial respiration in blood platelets in rats and human with dyslipidemia. Physiol Res 65:777-88.Human
Rat
Blood cells
Platelet
Puskarich 2016 J Crit Care2016Puskarich MA, Kline JA, Watts JA, Shirey K, Hosler J, Jones AE (2016) Early alterations in platelet mitochondrial function are associated with survival and organ failure in patients with septic shock. J Crit Care 31:63-7.HumanBlood cells
Platelet
Sepsis
Ehinger 2015 J Neurol2015Ehinger JK, Morota S, Hansson MJ, Paul G, Elmér E (2015) Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients. J Neurol 262:1493-503.HumanBlood cells
Lymphocyte
Platelet
Neurodegenerative
Other
Li 2015 Sci Rep2015Li P, Wang B, Sun F, Li Y, Li Q, Lang H, Zhao Z, Gao P, Zhao Y, Shang Q, Liu D, Zhu Z (2015) Mitochondrial respiratory dysfunctions of blood mononuclear cells link with cardiac disturbance in patients with early-stage heart failure. Sci Rep 5:10229.HumanBlood cells
Lymphocyte
Cardiovascular
De Lucas 2014 J Sports Sci2014De Lucas DR, Caputo F, Mendes de Souza K, Sigwalt AR, Ghisoni K, Lock Silveira PC, Remor AP, da Luz Scheffer D, Antonacci Guglielmo LG, Latini A (2014) Increased platelet oxidative metabolism, blood oxidative stress and neopterin levels after ultraendurance exercise. J Sports Sci 32:22-30HumanBlood cells
Platelet
Sjoevall 2014 PLoS One2014Sjövall F, Morota S, Asander Frostner E, Hansson Magnus J, Elmer E (2014) Cytokine and nitric oxide levels in patients with sepsis - temporal evolvement and relation to platelet mitochondrial respiratory function. PLoS One 9:e97673.HumanBlood cells
Platelet
Sepsis
Sonkar 2014 FASEB J2014Sonkar VK, Kulkarni PP, Dash D (2014) Amyloid beta peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization. FASEB J 28:1819-29.Human
Mouse
Blood cells
Platelet
Alzheimer's
Karabatsiakis 2014 Transl Psychiatry2014Karabatsiakis A, Boeck C, Salinas-Manrique J, Kolassa S, Calzia E, Dietrich DE, Kolassa IT (2014) Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression. Transl Psychiatry 4:e397.HumanBlood cellsNeurodegenerative
Cheng 2014 Science2014Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR6, Li Y, Ifrim DC, Arts RJ, van der Meer BM, Deen PM, Logie C, O'Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG (2014) mTOR- and HIF-1 α–mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684.HumanBlood cells
Other cell lines
Piel 2014 Acta Physiol (Oxf)2014Piel S, Ehinger JK, Elmér E, Hansson Magnus J (2014) Metformin induces lactate production in peripheral blood mononuclear cells and platelets through specific mitochondrial Complex I inhibition. Acta Physiol (Oxf) 213:171-80.HumanBlood cells
Other cell lines
Platelet
Diabetes
Karamercan 2013 Shock2013Karamercan MA, Weiss SL, Villarroel JP, Guan Y, Werlin E, Figueredo R, Becker LB, Sims C (2013) Can peripheral blood mononuclear cells be used as a proxy for mitochondrial dysfunction in vital organs during hemorrhagic shock and resuscitation? Shock 40:476-84.RatHeart
Liver
Kidney
Blood cells
Lymphocyte
Other
Sjoevall 2013 Crit Care2013Sjoevall F, Morota S, Persson J, Hansson Magnus J, Elmer E (2013) Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells. Crit Care 17:R152.HumanBlood cellsSepsis
Hroudova 2013 Mitochondrion2013Hroudová J, Fišar Z, Kitzlerová E, Zvěřová M, Raboch J (2013) Mitochondrial respiration in blood platelets of depressive patients. Mitochondrion 13:795-800.HumanBlood cells
Platelet
Neurodegenerative
Sjoevall 2013 Mitochondrion2013Sjövall F, Ehinger JK, Marelsson SE, Morota S, Asander Frostner E, Uchino H, Lundgren J, Arnbjörnsson E, Hansson Magnus J, Fellman V, Elmér E (2013) Mitochondrial respiration in human viable platelets - methodology and influence of gender, age and storage. Mitochondrion 13:7-14.HumanBlood cells
Platelet
Aging;senescence
Neurodegenerative
Perales Villarroel 2013 J Surg Res2013Perales Villarroel JP, Figueredo R, Guan Y, Tomaiuolo M, Karamercan MA, Welsh J, Selak MA, Becker LB, Sims C (2013) Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function. J Surg Res 184:422-9.HumanBlood cells
Platelet
Villarroel 2013 J Trauma Acute Care Surg2013Villarroel JP, Guan Y, Werlin E, Selak MA, Becker LB, Sims CA (2013) Hemorrhagic shock and resuscitation are associated with peripheral blood mononuclear cell mitochondrial dysfunction and immunosuppression. J Trauma Acute Care Surg 75:24-31.RatBlood cells
Lymphocyte
Other
Hroudova 2012 European Psychiatry2012Hroudova J, Fisar Z, Korabecny J, Kuca K, Jirak R, Raboch J (2012) P-451 - changes of cellular respiration in patients with Alzheimer's disease. European Psychiatry 27:01.HumanBlood cells
Platelet
Alzheimer's
Neurodegenerative
Usui 2012 Eur J Anaes2012Usui D, Isaksson M, Suzuki M, Sjovall F, Elmer E, Uchino H (2012) The influence of anesthetic agents on mitochondrial function as determined by high‐resolved respirometry of human blood cells: 9AP7‐9. Eur J Anaes 29:150.HumanBlood cells
Platelet
Leuner 2012 Mol Neurobiol2012Leuner K, Schulz K, Schütt T, Pantel J, Prvulovic D, Rhein V, Savaskan E, Czech C, Eckert A, Müller WE (2012) Peripheral mitochondrial dysfunction in Alzheimer's disease: focus on lymphocytes. Mol Neurobiol 46:194-204.HumanBlood cells
Lymphocyte
Aging;senescence
Alzheimer's
Neurodegenerative
Japiassu 2011 Crit Care Med2011Japiassu AM, Santiago AP, d'Avila Jda C, Garcia-Souza LF, Galina A, Castro Faria-Neto HC, Bozza FA, Oliveira MF (2011) Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5'-triphosphate synthase activity. Crit Care Med 39:1056-63.HumanBlood cellsSepsis
Sjoevall 2010 Crit Care2010Sjoevall F, Morota S, Hansson Magnus J, Friberg H, Gnaiger E, Elmer E (2010) Temporal increase of platelet mitochondrial respiration is negatively associated with clinical outcome in patients with sepsis. Crit Care 14:R214.HumanBlood cells
Platelet
Sepsis
» O2k-Publications: Blood cells
» O2k-Publications: Platelets


Picked up


Open questions

  • How does PLT activation influence ROUTINE, LEAK and ET capacity?
  • How is PBMC activation quantified and controlled, and how does it influence ROUTINE, LEAK and ET capacity?
  • How does 2-3 mM lactate influence respiration in MiR05, compared to 10 mM pyruvate?


Milestones

  • In progress (2018)
  • March 12: Edit template of MitoEAGLE blood cell data sheet and post on this website, send alert to coauthors (Erich, Zuzana).
  • March 12: Lund workshop circular (Eleonor / Marija) - invite further groups: Elisa Calabria, Kathrin Renner, Alexander Karabatriakis, Irene Pichler (contact US: Anthony Molina, Brian Irvin).
  • March 15: Prepare document on regulations for sensitive data (Chiara; waiting for expert-meeting)
  • March 16: Suggest topics for STSM to generate experimental data blocks for this manuscript (send to Magda).
  • March 16-31: Send reminder to fill MitoEAGLE blood cell data sheets and send to Innsbruck, specify 'Open Access' (MitoEAGLE data bank on wiki), or to be shared with coauthors.
  • April 1-30: Send reminder to write Table and Figure blocks and send to Innsbruck.
  • April 1st week: Meeting with Anthony Molina in Innsbruck.
  • April 30: MitoEAGLE workprint Version 01 - manuscript blocks arranged in work flow.
» May 28-30: MitoEAGLE Lund 2018
  • Achieved (2019)
» Mar 11-14: MitoEAGLE WG4 Matrei a. Brenner 2019-03
  • Achieved (2018)
» May 28-30: MitoEAGLE Lund 2018
» Feb 21-23: MitoEAGLE Poznan 2018
» Jan 29-Feb 1: MitoEAGLE Innsbruck 2018


Publication

A Working Group of the COST Action MitoEAGLE is preparing a manuscript 'Interlaboratory guide through procedures for mitochondrial respiratory studies with living and permeabilized peripheral blood mononuclear cells and platelets'. The group is working on it with Open Access as a ‘MitoEAGLE preprint’ and the ultimate aim of publication in a scientific journal.
Compare: Gnaiger 2019 MitoFit Preprint Arch

Coauthors

The present alphabetical list of coauthors icludes all actively involved participants of MitoEAGLE Innsbruck 2018 and MitoEAGLE Poznan 2018 and will be extended by further contributors at MitoEAGLE Lund 2018 and by MitoEAGLE members submitting their valuable contributions. All coauthors will have to confirm to have made a contribution and to have read the final manuscript.

Publication strategy

  • Data linked to published papers or manuscripts in press are superior to unpublished data.
  • Inclusion of unpublished data should not block independent publication by the indivudual teams.
  • Data classified as occasional observations or preliminary results are statistically valuable when combined with comparable data from other groups - pull out your unpublished observations (data).
Acknowledgements: We thank M. Beno for management assistance, and Engin Ayse Basak for stimulating discussions. This publication is based upon work from COST Action CA15203 MitoEAGLE, supported by COST (European Cooperation in Science and Technology), and K-Regio project MitoFit (E.G.).


Labels: MiParea: Respiration, Instruments;methods, mtDNA;mt-genetics, nDNA;cell genetics, Gender  Pathology: Aging;senescence 

Organism: Human  Tissue;cell: Blood cells, Platelet  Preparation: Intact cells, Permeabilized cells  Enzyme: Marker enzyme 

Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: F, N, S, Gp, CIV, NS, Other combinations, ROX 


MitoFitPublication, MitoEAGLEPublication, PBMCs