{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:24:29Z","timestamp":1792650269320,"version":"4.5.0"},"reference-count":127,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Analysis of the function, structure, and intracellular organization of mitochondria is important for elucidating energy metabolism and intracellular energy transfer. In addition, basic and clinically oriented studies that investigate organ\/tissue\/cell dysfunction in various human diseases, including myopathies, cardiac\/brain ischemia-reperfusion injuries, neurodegenerative diseases, cancer, and aging, require precise estimation of mitochondrial function. It should be noted that the main metabolic and functional characteristics of mitochondria obtained in situ (in permeabilized cells and tissue samples) and in vitro (in isolated organelles) are quite different, thereby compromising interpretations of experimental and clinical data. These differences are explained by the existence of the mitochondrial network, which possesses multiple interactions between the cytoplasm and other subcellular organelles. Metabolic and functional crosstalk between mitochondria and extra-mitochondrial cellular environments plays a crucial role in the regulation of mitochondrial metabolism and physiology. Therefore, it is important to analyze mitochondria in vivo or in situ without their isolation from the natural cellular environment. This review summarizes previous studies and discusses existing approaches and methods for the analysis of mitochondrial function, structure, and intracellular organization in situ.<\/jats:p>","DOI":"10.3390\/ijms23042252","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:18:05Z","timestamp":1645431485000},"page":"2252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Analysis of Mitochondrial Function, Structure, and Intracellular Organization In Situ in Cardiomyocytes and Skeletal Muscles"],"prefix":"10.3390","volume":"23","author":[{"given":"Andrey V.","family":"Kuznetsov","sequence":"first","affiliation":[{"name":"Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria"},{"name":"Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7024-5383","authenticated-orcid":false,"given":"Sabzali","family":"Javadov","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR 00936-5067, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimund","family":"Margreiter","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1396-3407","authenticated-orcid":false,"given":"Judith","family":"Hagenbuchner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1015-2302","authenticated-orcid":false,"given":"Michael J.","family":"Ausserlechner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0092-8674(03)00116-8","article-title":"Mitochondria: Releasing power for life and unleashing the machineries of death","volume":"112","author":"Newmeyer","year":"2003","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R551","DOI":"10.1016\/j.cub.2006.06.054","article-title":"Mitochondria: More than Just a Powerhouse","volume":"16","author":"McBride","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nrm2153","article-title":"The apoptosome: Signalling platform of cell death","volume":"8","author":"Riedl","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/74994","article-title":"Mitochondrial control of cell death","volume":"6","author":"Kroemer","year":"2000","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0968-0004(00)01745-X","article-title":"A mitochondrial perspective on cell death","volume":"26","author":"Bernardi","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nprot.2014.018","article-title":"Comprehensive measurement of respiratory activity in permeabilized cells using extracellular flux analysis","volume":"9","author":"Salabei","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature12985","article-title":"Mitochondrial form and function","volume":"505","author":"Jonathan","year":"2014","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.tcb.2018.02.009","article-title":"Endoplasmic Reticulum-Mitochondrial Contactology: Structure and Signaling Functions","volume":"28","author":"Weaver","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.bbabio.2008.11.012","article-title":"Measurements of mitochondrial calcium in vivo","volume":"1787","author":"Pozzan","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1016\/S0006-3495(98)77642-8","article-title":"Role of Mitochondria in Calcium Regulation of Spontaneously Contracting Cardiac Muscle Cells","volume":"75","author":"Bowser","year":"1998","journal-title":"Biophys. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1126\/science.280.5370.1763","article-title":"Close Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca2+ Responses","volume":"280","author":"Rizzuto","year":"1998","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11401","DOI":"10.1074\/jbc.273.19.11401","article-title":"Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss","volume":"273","author":"Cai","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1038\/s41598-018-21519-2","article-title":"Very long-\/ and long Chain-3-Hydroxy Acyl CoA Dehydrogenase Deficiency correlates with deregulation of the mitochondrial fusion\/fission machinery","volume":"8","author":"Hagenbuchner","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4909","DOI":"10.7150\/thno.33758","article-title":"Modulation of Respiration and Mitochondrial Dynamics by SMAC-Mimetics for Combination Therapy in Chemoresistant Cancer","volume":"9","author":"Hagenbuchner","year":"2019","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1038\/onc.2015.264","article-title":"BIRC5\/Survivin as a target for glycolysis inhibition in high-stage neuroblastoma","volume":"35","author":"Hagenbuchner","year":"2016","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.bbabio.2009.01.019","article-title":"Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells","volume":"1787","author":"Griffiths","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.tcb.2008.01.006","article-title":"Mitochondria in cancer cells: What is so special about them?","volume":"18","author":"Gogvadze","year":"2008","journal-title":"Trends Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00075197-200011000-00009","article-title":"Mitochondria and ageing","volume":"3","author":"Cottrell","year":"2000","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.yjmcc.2014.03.011","article-title":"Mitochondrial reactive oxygen species production and elimination","volume":"73","author":"Nickel","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1113\/jphysiol.2003.049478","article-title":"Mitochondrial formation of reactive oxygen species","volume":"552","author":"Turrens","year":"2003","journal-title":"J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00018.2001","article-title":"Free Radicals in the Physiological Control of Cell Function","volume":"82","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1083\/jcb.141.6.1423","article-title":"The Regulation of Reactive Oxygen Species Production during Programmed Cell Death","volume":"141","author":"Tan","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/978-981-13-8367-0_10","article-title":"Quantification of Mitochondrial Network Characteristics in Health and Disease","volume":"1158","author":"Valente","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"83","DOI":"10.9734\/bpi\/nfmmr\/v16\/1816C","article-title":"ROS Flashes in Mitochondria Occur Concomitantly with Inner Mitochondrial Membrane Depolarization and Mitochondrial Calcium Sparks","volume":"16","author":"Kuznetsov","year":"2021","journal-title":"New Front. Med. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"ref_28","first-page":"3","article-title":"Isolation of Mitochondria from Tissues and Cells by Differential Centrifugation","volume":"34","author":"Graham","year":"1999","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nprot.2006.478","article-title":"Organelle isolation: Functional mitochondria from mouse liver, muscle and cultured filroblasts","volume":"2","author":"Frezza","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-1-61779-504-6_5","article-title":"Measurement of Mitochondrial Oxygen Consumption Using a Clark Electrode","volume":"837","author":"Li","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2257-4_1","article-title":"Preparation of \u201cfunctional\u201d mitochondria: A challenging business","volume":"1264","author":"Lehr","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0958-1669(02)00008-3","article-title":"Advances in the analysis of single mitochondria","volume":"14","author":"Fuller","year":"2003","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nprot.2008.61","article-title":"Analysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells","volume":"3","author":"Kuznetsov","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/biof.5520070312","article-title":"Use of saponin-permeabilized muscle fibers for the diagnosis of mitochondrial diseases","volume":"7","author":"Kuznetsov","year":"1998","journal-title":"BioFactors"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/0005-2728(93)90029-F","article-title":"Functional characterization of mitochondrial oxidative phosphorylation in saponin-skinned human muscle fibers","volume":"1144","author":"Kunz","year":"1993","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1023\/A:1006834912257","article-title":"Permeabilized cell and skinned fiber techniques in studies of mitochondrial function in vivo","volume":"184","author":"Saks","year":"1998","journal-title":"Mol. Cell Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1113\/eph8802511","article-title":"Possible Role of Cytoskeleton in Intracellular Arrangement and Regulation of Mitochondria","volume":"88","author":"Appaix","year":"2003","journal-title":"Exp. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1083\/jcb.140.5.1091","article-title":"Functional Imaging of Mitochondria in Saponin-permeabilized Mice Muscle Fibers","volume":"140","author":"Kuznetsov","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.bbabio.2006.03.014","article-title":"Mitochondrial subpopulations and heterogeneity revealed by confocal imaging: Possible physiological role?","volume":"1757","author":"Kuznetsov","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1073\/pnas.95.4.1618","article-title":"Subcellular metabolic transients and mitochondrial redox waves in heart cells","volume":"95","author":"Romashko","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ymeth.2008.09.025","article-title":"Chemical calcium indicators","volume":"46","author":"Paredes","year":"2008","journal-title":"Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.bbabio.2017.03.001","article-title":"Synchronism in mitochondrial ROS flashes, membrane depolarization and calcium sparks in human carcinoma cells","volume":"1858","author":"Kuznetsov","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenergy"},{"key":"ref_43","first-page":"145","article-title":"Ultra-high resolution scanning electron microscopic studies on the sarcoplasmic reticulum and mitochondria in various muscles: A review","volume":"7","author":"Ogata","year":"1993","journal-title":"Scanning Microsc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.yjmcc.2011.08.030","article-title":"Measuring mitochondrial function in intact cardiac myocytes","volume":"52","author":"Dedkova","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_45","first-page":"e2431","article-title":"Respirometric Oxidative Phosphorylation Assessment in Saponin-permeabilized Cardiac Fibers","volume":"48","author":"Hughey","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-0716-1653-6_7","article-title":"Assessment of Respiratory Enzymes in Intact Cells by Permeabilization with Alamethicin","volume":"2363","author":"Rasmusson","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/978-1-4939-7720-8_11","article-title":"Determination of Mitochondrial Oxygen Consumption in the Retina Ex Vivo: Applications for Retinal Disease","volume":"1753","author":"Adlakha","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0091-679X(01)65007-6","article-title":"In vivo measurements of respiration control by cytochrome c oxidase and in situ analysis of oxidative phosphorylation","volume":"65","author":"Villani","year":"2001","journal-title":"Methods Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1046-2023(02)00036-1","article-title":"In vivo and in organello assessment of OXPHOS activities","volume":"26","author":"Barrientos","year":"2002","journal-title":"Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jneumeth.2004.02.027","article-title":"Method for in situ detection of the mitochondrial function in neurons","volume":"137","author":"Safiulina","year":"2004","journal-title":"J. Neurosci. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1373\/clinchem.2009.131441","article-title":"High-Throughput Assay to Measure Oxygen Consumption in Digitonin-Permeabilized Cells of Patients with Mitochondrial Disorders","volume":"56","author":"Jonckheere","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0021-9258(19)57190-3","article-title":"Respiratory enzymes in oxidative phosphorylation. II. Difference spectra","volume":"217","author":"Chance","year":"1955","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0021-9258(18)65266-4","article-title":"Respiratory enzymes in oxidative phosphorylation. VI. The effects of adenosine diphosphate on azide-treated mitochondria","volume":"221","author":"Chance","year":"1956","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1023\/A:1024437201166","article-title":"Mitochondrial oxidative phosphorylation: Pitfalls and tips in measuring and interpreting enzyme activities","volume":"26","author":"Chretien","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0091-679X(06)80001-4","article-title":"Isolation and Subfractionation of Mitochondria from Animal Cells and Tissue Culture Lines","volume":"80","author":"Pallotti","year":"2007","journal-title":"Rev. Methods Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/j.biocel.2009.04.003","article-title":"Structural and functional organization of the mitochondrial respiratory chain: A dynamic super-assembly","volume":"41","author":"Lenaz","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0091-679X(06)80005-1","article-title":"Polarographic Assays of Respiratory Chain Complex Activity","volume":"80","author":"Villani","year":"2007","journal-title":"Methods Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/9780470110355.ch1","article-title":"Oxygen Electrode Measurements in Biochemical Analysis","volume":"17","author":"Lessler","year":"1969","journal-title":"Methods Biochem. Anals"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/j.1474-9726.2010.00628.x","article-title":"Mitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibers","volume":"9","author":"Picard","year":"2010","journal-title":"Aging Cell"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Picard, M., Taivassalo, T., Ritchie, D., Wright, K.J., Thomas, M.M., Romestaing, C., and Hepple, R.T. (2011). Mitochondrial Structure and Function Are Disrupted by Standard Isolation Methods. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018317"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1023\/A:1006843113166","article-title":"Cytoskeleton and mitochondrial morphology and function","volume":"184","author":"Rappaport","year":"1998","journal-title":"Mol. Cell. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0091-679X(06)80034-8","article-title":"Analysis of protein-protein interactions in mitochondria","volume":"80","author":"Johannes","year":"2007","journal-title":"Methods Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.bbamem.2011.12.034","article-title":"Regulation of respiration in muscle cells in vivo by VDAC through interaction with the cytoskeleton and Mt, CK within Mitochondrial Interactosome","volume":"1818","author":"Guzun","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1083\/jcb.150.6.1283","article-title":"Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function","volume":"150","author":"Milner","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.1093\/hmg\/ddv184","article-title":"Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle","volume":"24","author":"Winter","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev.ph.41.030179.002413","article-title":"Mitochondrial Function in the Heart","volume":"41","author":"Williamson","year":"1979","journal-title":"Annu. Rev. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"C377","DOI":"10.1152\/ajpcell.1990.258.3.C377","article-title":"Regulation of oxidative phosphorylation in the mammalian cell","volume":"258","author":"Balaban","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/0005-2728(94)90124-4","article-title":"Function of the outer mitochondrial compartment in regulation of energy metabolism","volume":"1187","author":"Brdiczka","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1111\/j.1432-1033.1996.00909.x","article-title":"Striking difference between slow and fast twitch muscles in the kinetics of regulation of respiration by ADP in the cells in vivo","volume":"241","author":"Kuznetsov","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"C399","DOI":"10.1152\/ajpcell.1997.272.2.C399","article-title":"ADP-regenerating enzyme systems in mitochondria of guinea pig myometrium and heart","volume":"272","author":"Clark","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.yjmcc.2011.07.015","article-title":"Intracellular Energetic Units regulate metabolism in cardiac cells","volume":"52","author":"Saks","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1161\/hh1401.093440","article-title":"Energetic crosstalk between organelles: Architectural integration of energy production and utilization","volume":"89","author":"Kaasik","year":"2001","journal-title":"Circ. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-1-61779-382-0_3","article-title":"High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle","volume":"810","author":"Pesta","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-7831-1_3","article-title":"High-Resolution Fluo, Respirometry and OXPHOS Protocols for Human Cells, Permeabilized Fibers from Small Biopsies of Muscle, and Isolated Mitochondria","volume":"1782","author":"Doerrier","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_75","first-page":"207","article-title":"High-resolution respirometry with multiple substrates titration in permeabilized myocardial fibers","volume":"116","author":"Duicu","year":"2012","journal-title":"Rev. Med.-Chirurg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S0008-6363(01)00552-1","article-title":"Fatty acid metabolism in cardiac failure: Biochemical, genetic and cellular analysis","volume":"54","author":"Goldenthal","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"H1633","DOI":"10.1152\/ajpheart.00701.2003","article-title":"Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion","volume":"286","author":"Kuznetsov","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kuznetsov, A.V., Javadov, S., Margreiter, R., Grimm, M., Hagenbuchner, J., and Ausserlechner, M.J. (2019). The Role of Mitochondria in the Mechanisms of Cardiac Ischemia-Reperfusion Injury. Antioxidants, 8.","DOI":"10.3390\/antiox8100454"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"21629","DOI":"10.1074\/jbc.271.35.21629","article-title":"Loss of Function of Cytochrome c in Jurkat Cells Undergoing Fas-mediated Apoptosis","volume":"271","author":"Krippner","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.bbabio.2008.03.019","article-title":"Distinct organization of energy metabolism in HL-1 cardiac cell line and cardiomyocytes","volume":"1777","author":"Eimre","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0022-2828(89)90839-0","article-title":"Quantitative evaluation of relationship between cardiac energy metabolism and post-ischemic recovery of contractile function","volume":"21","author":"Saks","year":"1989","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/0003-9861(83)90445-9","article-title":"Effects of SH group reagents on creatine kinase interaction with the mitochondrial membrane","volume":"220","author":"Font","year":"1983","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/978-1-4939-9027-6_18","article-title":"Using Seahorse Machine to Measure OCR and ECAR in Cancer Cells","volume":"1928","author":"Zhang","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Clerc, P., and Polster, B.M. (2012). Investigation of Mitochondrial Dysfunction by Sequential Microplate-Based Respiration Measurements from Intact and Permeabilized Neurons. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034465"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/978-1-4939-3810-0_23","article-title":"Analysis of Aerobic Respiration in Intact Skeletal Muscle Tissue by Microplate-Based Respirometry","volume":"1460","author":"Shintaku","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/B978-0-12-801415-8.00016-3","article-title":"Analysis and Interpretation of Microplate-Based Oxygen Consumption and p, H Data","volume":"547","author":"Divakaruni","year":"2014","journal-title":"Methods Enzymol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/cptx.3","article-title":"Fluorescence-Based Microplate Assays for In Vitro Assessment of Mitochondrial Toxicity, Metabolic Perturbation, and Cellular Oxygenation","volume":"70","author":"Hynes","year":"2016","journal-title":"Curr. Protoc. Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1093\/emboj\/21.7.1616","article-title":"Mitochondria are morphologically and functionally heterogeneous within cells","volume":"21","author":"Collins","year":"2002","journal-title":"EMBO J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.3390\/ijms10041911","article-title":"Heterogeneity of Mitochondria and Mitochondrial Function within Cells as Another Level of Mitochondrial Complexity","volume":"10","author":"Kuznetsov","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_90","first-page":"2313","article-title":"Mitochondria dynamism: Of shape, transport and cell migration","volume":"71","author":"Mariotti","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1016\/j.biocel.2009.03.007","article-title":"The cell-type specificity of mitochondrial dynamics","volume":"41","author":"Kuznetsov","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1582-4934.2009.00750.x","article-title":"Complex patterns of mitochondrial dynamics in human pancreatic cells revealed by fluorescent confocal imaging","volume":"14","author":"Kuznetsov","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0005-2728(03)00108-7","article-title":"Mitochondrial potassium transport: The K+ cycle","volume":"1606","author":"Garlid","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1152\/physrev.00021.2013","article-title":"Mitochondrial Channels: Ion Fluxes and More","volume":"94","author":"Szabo","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ceca.2012.03.003","article-title":"Regulation of ATP production by mitondrial Ca(2+)","volume":"52","author":"Tarasov","year":"2012","journal-title":"Cell Calcium"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1042\/bst0220522","article-title":"Regulation of mitochondrial metabolism through changes in matrix volume","volume":"22","author":"Halestrap","year":"1994","journal-title":"Biochem. Soc. Trans."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0005-2728(98)00122-4","article-title":"Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart","volume":"1366","author":"Halestrap","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1124\/jpet.109.153213","article-title":"Mitochondrial Permeability Transition Pore Opening as a Promising Therapeutic Target in Cardiac Diseases","volume":"330","author":"Javadov","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/0003-9861(79)90372-2","article-title":"The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site","volume":"195","author":"Haworth","year":"1979","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Javadov, S., Kozlov, A.V., and Camara, A.K.S. (2020). Mitochondria in Health and Diseases. Cells, 9.","DOI":"10.3390\/cells9051177"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.mito.2017.08.004","article-title":"Different approaches to modeling analysis of mitochondrial swelling","volume":"38","author":"Javadov","year":"2018","journal-title":"Mitochondrion"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"20474","DOI":"10.1074\/jbc.M001077200","article-title":"Concentration-dependent Effects of Nitric Oxide on Mitochondrial Permeability Transition and Cytochrome cRelease","volume":"275","author":"Brookes","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Dubinin, M.V., Starinets, V.S., Talanov, E.Y., Mikheeva, I.B., Belosludtseva, N.V., and Belosludtsev, K.N. (2021). Alisporivir Improves Mitochondrial Function in Skeletal Muscle of mdx Mice but Suppresses Mitochondrial Dynamics and Biogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189780"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000445616","article-title":"The Effect of NO Donor on Calcium Uptake and Reactive Nitrogen Species Production in Mitochondria","volume":"39","author":"Akopova","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/978-1-61779-382-0_13","article-title":"Use of a Calcium-Sensitive Electrode for Studies on Mitochondrial Calcium Transport","volume":"810","author":"Moreno","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Belosludtsev, K.N., Talanov, E.Y., Starinets, V.S., Agafonov, A.V., Dubinin, M.V., and Belosludtseva, N.V. (2019). Transport of Ca2+ and Ca2+-Dependent Permeability Transition in Rat Liver Mitochondria under the Streptozotocin-Induced Type I Diabetes. Cells, 8.","DOI":"10.3390\/cells8091014"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.yjmcc.2004.10.007","article-title":"NHE-1 inhibition improves impaired mitochondrial permeability transition and respiratory function during postinfarction remodelling in the rat","volume":"38","author":"Javadov","year":"2005","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11010-006-9192-9","article-title":"Short Term Training Attenuates Opening of the Mitochondrial Permeability Transition Pore Without Affecting Myocardial Function Following Ischemia-Reperfusion","volume":"291","author":"Ciminelli","year":"2006","journal-title":"Mol. Cell. Biochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1042\/bj3070093","article-title":"Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion","volume":"307","author":"Griffiths","year":"1995","journal-title":"Biochem. J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1113\/jphysiol.2003.034231","article-title":"Ischaemic Preconditioning Inhibits Opening of Mitochondrial Permeability Transition Pores in the Reperfused Rat Heart","volume":"549","author":"Javadov","year":"2003","journal-title":"J. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S0008-6363(99)00365-X","article-title":"Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition","volume":"45","author":"Javadov","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0006-3495(99)77239-5","article-title":"Transient and long-lasting openings of the mitochondrial permeability transition pore can be monitored directly in intact cells by changes in mitochondrial calcein fluorescence","volume":"76","author":"Petronilli","year":"1999","journal-title":"Biophys. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/jcmm.12220","article-title":"Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in cardiomyocytes: The role of mitochondria","volume":"18","author":"Hernandez","year":"2014","journal-title":"J. Cell Mol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1097\/ALN.0000000000000876","article-title":"Involvement of Cyclophilin D and Calcium in Isoflurane-induced Preconditioning","volume":"123","author":"Teixeira","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1046\/j.1432-1033.2002.03087.x","article-title":"Detecting mitochondrial permeability transition by confocal imaging of intact cells pinocytically loaded with calcein","volume":"269","author":"Jones","year":"2002","journal-title":"Eur. J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0005-2728(98)00112-1","article-title":"The mitochondrial permeability transition in cell death: A common mechanism in necrosis, apoptosis and autophagy","volume":"1366","author":"Lemasters","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"15282","DOI":"10.1074\/jbc.RA119.009477","article-title":"A modified calcium retention capacity assay clarifies the roles of extra- and intracellular calcium pools in mitochondrial permeability transition pore opening","volume":"294","author":"Harisseh","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3389\/fphys.2021.773839","article-title":"Analysis of Mitochondrial Calcium Retention Capacity in Cultured Cells: Permeabilized Cells Versus Isolated Mitochondria","volume":"12","author":"Jang","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1768-322X.1986.tb00458.x","article-title":"Mitochondrial analysis in living cells: The use of rhodamine 123 and flow cytometry","volume":"57","author":"Ronot","year":"1986","journal-title":"Biol. Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0091-679X(08)60190-9","article-title":"Fluorescent Labeling of Mitochondria","volume":"29","author":"Chen","year":"1988","journal-title":"Methods Cell Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1097\/01.TP.0000115346.85679.34","article-title":"Functional heterogeneity of mitochondria after cardiac cold ischemia and reperfusion revealed by confocal imaging","volume":"77","author":"Kuznetsov","year":"2004","journal-title":"Transplantation"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/acel.12102","article-title":"Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice","volume":"12","author":"Siegel","year":"2013","journal-title":"Aging Cell"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1074\/jbc.M009093200","article-title":"Selective targeting of a redox-active ubiquinone to mitochondria within cells: Antioxidant and antiapoptotic properties","volume":"276","author":"Kelso","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"39469","DOI":"10.18632\/oncotarget.5783","article-title":"Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats","volume":"6","author":"Javadov","year":"2015","journal-title":"Oncotarget"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.18632\/aging.100404","article-title":"Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents","volume":"3","author":"Anisimov","year":"2011","journal-title":"Aging"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6859523","DOI":"10.1155\/2016\/6859523","article-title":"Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases","volume":"2016","author":"Zhang","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2174\/1874609809666160921113706","article-title":"Cellular and Molecular Mechanisms of Action of Mitochondria-Targeted Antioxidants","volume":"10","author":"Feniouk","year":"2017","journal-title":"Curr. Aging Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:22:03Z","timestamp":1760134923000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":127,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23042252"],"URL":"https:\/\/doi.org\/10.3390\/ijms23042252","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]}}}