{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:11:09Z","timestamp":1789175469578,"version":"build-2803163510"},"reference-count":74,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD092550-01"],"award-info":[{"award-number":["R01HD092550-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["PFI-TT-1827309"],"award-info":[{"award-number":["PFI-TT-1827309"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["PHY-2013874"],"award-info":[{"award-number":["PHY-2013874"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-2052305"],"award-info":[{"award-number":["MCB-2052305"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["PHY-1748958"],"award-info":[{"award-number":["PHY-1748958"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R25GM067110"],"award-info":[{"award-number":["R25GM067110"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000936","name":"Gordon and Betty Moore Foundation","doi-asserted-by":"publisher","award":["2919.02"],"award-info":[{"award-number":["2919.02"]}],"id":[{"id":"10.13039\/100000936","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1764269"],"award-info":[{"award-number":["1764269"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,11,19]]},"abstract":"<jats:p>Mitochondrial metabolism is of central importance to diverse aspects of cell and developmental biology. Defects in mitochondria are associated with many diseases, including cancer, neuropathology, and infertility. Our understanding of mitochondrial metabolism in situ and dysfunction in diseases are limited by the lack of techniques to measure mitochondrial metabolic fluxes with sufficient spatiotemporal resolution. Herein, we developed a new method to infer mitochondrial metabolic fluxes in living cells with subcellular resolution from fluorescence lifetime imaging of NADH. This result is based on the use of a generic coarse-grained NADH redox model. We tested the model in mouse oocytes and human tissue culture cells subject to a wide variety of perturbations by comparing predicted fluxes through the electron transport chain (ETC) to direct measurements of oxygen consumption rate. Interpreting the fluorescence lifetime imaging microscopy measurements of NADH using this model, we discovered a homeostasis of ETC flux in mouse oocytes: perturbations of nutrient supply and energy demand of the cell do not change ETC flux despite significantly impacting NADH metabolic state. Furthermore, we observed a subcellular spatial gradient of ETC flux in mouse oocytes and found that this gradient is primarily a result of a spatially heterogeneous mitochondrial proton leak. We concluded from these observations that ETC flux in mouse oocytes is not controlled by energy demand or supply, but by the intrinsic rates of mitochondrial respiration.<\/jats:p>","DOI":"10.7554\/elife.73808","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T07:15:10Z","timestamp":1637565310000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.73808","source":"Crossref","is-referenced-by-count":32,"title":["A coarse-grained NADH redox model enables inference of subcellular metabolic fluxes from fluorescence lifetime imaging"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5798-4448","authenticated-orcid":true,"given":"Xingbo","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cellular Biology and John A. Paulson School of Engineering and Applied Sciences, Harvard University","place":["Cambridge, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4076-5337","authenticated-orcid":true,"given":"Gloria","family":"Ha","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cellular Biology and John A. Paulson School of Engineering and Applied Sciences, Harvard University","place":["Cambridge, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Needleman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cellular Biology and John A. Paulson School of Engineering and Applied Sciences, Harvard University","place":["Cambridge, United States"]},{"name":"Center for Computational Biology, Flatiron Institute","place":["New York, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1093\/molehr\/gaz055","article-title":"The spatio-temporal dynamics of mitochondrial membrane potential during oocyte maturation","volume":"25","author":"Al-Zubaidi","year":"2019","journal-title":"Molecular Human Reproduction"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00718","article-title":"Mitochondrial Heterogeneity","volume":"9","author":"Aryaman","year":"2018","journal-title":"Frontiers in Genetics"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0010036","article-title":"A biophysical model of the mitochondrial respiratory system and oxidative phosphorylation","volume":"1","author":"Beard","year":"2005","journal-title":"PLOS Computational Biology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.1365-2818.2012.03618.x","article-title":"Fluorescence lifetime imaging--techniques and applications","volume":"247","author":"Becker","year":"2012","journal-title":"Journal of Microscopy"},{"key":"bib5","volume-title":"The Bh TCSPC Handbook","author":"Becker","year":"2019"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nmeth.1288","article-title":"A genetically encoded fluorescent reporter of ATP:ADP ratio","volume":"6","author":"Berg","year":"2009","journal-title":"Nature Methods"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1038\/s41592-019-0582-9","article-title":"ilastik: interactive machine learning for (bio)image analysis","volume":"16","author":"Berg","year":"2019","journal-title":"Nature Methods"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/s1472-6483(10)61615-x","article-title":"The development of fertilized human ova to the blastocyst stage in KSOM(AA) medium: is a two-step protocol necessary?","volume":"5","author":"Biggers","year":"2002","journal-title":"Reproductive Biomedicine Online"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"8766","DOI":"10.1158\/0008-5472.CAN-04-3922","article-title":"Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH","volume":"65","author":"Bird","year":"2005","journal-title":"Cancer Research"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4936","article-title":"Separating NADH and NADPH fluorescence in live cells and tissues using FLIM","volume":"5","author":"Blacker","year":"2014","journal-title":"Nature Communications"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"The Biochemical Journal"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1172\/JCI64125","article-title":"The role of mitochondria in aging","volume":"123","author":"Bratic","year":"2013","journal-title":"The Journal of Clinical Investigation"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-017-1310-z","article-title":"Quantifying the cellular NAD+ metabolome using a tandem liquid chromatography mass spectrometry approach","volume":"14","author":"Bustamante","year":"2017","journal-title":"Metabolomics"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S0021-9258(19)57189-7","article-title":"RESPIRATORY ENZYMES IN OXIDATIVE PHOSPHORYLATION","volume":"217","author":"Chance","year":"1955","journal-title":"Journal of Biological Chemistry"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014820","article-title":"Modeling of mitochondria bioenergetics using a composable chemiosmotic energy transduction rate law: theory and experimental validation","volume":"6","author":"Chang","year":"2011","journal-title":"PLOS ONE"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108676","article-title":"On the dynamics of the adenylate energy system: homeorhesis vs homeostasis","volume":"9","author":"De la Fuente","year":"2014","journal-title":"PLOS ONE"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.cmet.2017.06.021","article-title":"Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake","volume":"26","author":"D\u00edaz-Garc\u00eda","year":"2017","journal-title":"Cell Metabolism"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.64821","article-title":"The distinct roles of calcium in rapid control of neuronal glycolysis and the tricarboxylic acid cycle","volume":"10","author":"D\u00edaz-Garc\u00eda","year":"2021","journal-title":"eLife"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1242\/dev.01181","article-title":"Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production","volume":"131","author":"Dumollard","year":"2004","journal-title":"Development"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0070-2153(06)77002-8","article-title":"The role of mitochondrial function in the oocyte and embryo","volume":"77","author":"Dumollard","year":"2007","journal-title":"Current Topics in Developmental Biology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.drudis.2007.12.008","article-title":"Advances in measuring cellular bioenergetics using extracellular flux","volume":"13","author":"Ferrick","year":"2008","journal-title":"Drug Discovery Today"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.1201\/b17427","volume-title":"Natural Biomarkers for Cellular Metabolism Biology, Techniques, and Applications","author":"Ghukasyan","year":"2015"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/s0005-2728(98)00076-0","article-title":"Mitochondrial respiration in the low oxygen environment of the cell. Effect of ADP on oxygen kinetics","volume":"1365","author":"Gnaiger","year":"1998","journal-title":"Biochimica et Biophysica Acta"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"241","DOI":"10.2217\/bmm.10.1","article-title":"Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies","volume":"4","author":"Heikal","year":"2010","journal-title":"Biomarkers in Medicine"},{"key":"bib25","volume-title":"Free Energy Transduction in Biology","author":"Hill","year":"1977"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1002\/(SICI)1098-2795(199608)44:4<476::AID-MRD7>3.0.CO;2-I","article-title":"Oxygen consumption and energy metabolism of the early mouse embryo","volume":"44","author":"Houghton","year":"1996","journal-title":"Molecular Reproduction and Development"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"15651","DOI":"10.1073\/pnas.0904764106","article-title":"Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators","volume":"106","author":"Imamura","year":"2009","journal-title":"PNAS"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1016\/S0006-3495(02)73945-3","article-title":"Kinetics of electron transfer through the respiratory chain","volume":"83","author":"Jin","year":"2002","journal-title":"Biophysical Journal"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/0014-5793(86)81542-3","article-title":"Two rules of enzyme kinetics for reversible Michaelis-Menten mechanisms","volume":"208","author":"Keleti","year":"1986","journal-title":"FEBS Letters"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/s0301-4622(01)00184-3","article-title":"A model of oxidative phosphorylation in mammalian skeletal muscle","volume":"92","author":"Korzeniewski","year":"2001","journal-title":"Biophysical Chemistry"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-46312-4","volume-title":"Principles of Fluorescence Spectroscopy","author":"Lakowicz","year":"2006"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1095\/biolreprod62.1.16","article-title":"Lactate regulates pyruvate uptake and metabolism in the preimplantation mouse embryo","volume":"62","author":"Lane","year":"2000","journal-title":"Biology of Reproduction"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13008-016-0015-4","article-title":"Mitochondria-cytoskeleton associations in mammalian cytokinesis","volume":"11","author":"Lawrence","year":"2016","journal-title":"Cell Division"},{"key":"bib34","doi-asserted-by":"publisher","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":"bib35","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aap9302","article-title":"Mapping metabolic changes by noninvasive, multiparametric, high-resolution imaging using endogenous contrast","volume":"4","author":"Liu","year":"2018","journal-title":"Science Advances"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1530\/rep.1.00703","article-title":"Respiration rates of individual bovine in vitro-produced embryos measured with a novel, non-invasive and highly sensitive microsensor system","volume":"130","author":"Lopes","year":"2005","journal-title":"Reproduction"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1126\/science.1104343","article-title":"Mitochondrial dysfunction and type 2 diabetes","volume":"307","author":"Lowell","year":"2005","journal-title":"Science"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1089\/ars.2017.7014","article-title":"Extraction and Quantitation of Nicotinamide Adenine Dinucleotide Redox Cofactors","volume":"28","author":"Lu","year":"2018","journal-title":"Antioxidants & Redox Signaling"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48107-2","article-title":"Label-free assessment of pre-implantation embryo quality by the Fluorescence Lifetime Imaging Microscopy (FLIM)-phasor approach","volume":"9","author":"Ma","year":"2019","journal-title":"Scientific Reports"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1242\/jcs.144337","article-title":"Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation","volume":"127","author":"MacVicar","year":"2014","journal-title":"Journal of Cell Science"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49178","article-title":"Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell","volume":"9","author":"Mick","year":"2020","journal-title":"eLife"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"5146","DOI":"10.1021\/ja01552a034","article-title":"Kinetics of the Reversible Michaelis-Menten Mechanism and the Applicability of the Steady-state Approximation 1","volume":"80","author":"Miller","year":"2002","journal-title":"Journal of the American Chemical Society"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/191144a0","article-title":"Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism","volume":"191","author":"Mitchell","year":"1961","journal-title":"Nature"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"7189","DOI":"10.1074\/jbc.M116.774471","article-title":"Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements","volume":"292","author":"Mookerjee","year":"2017","journal-title":"The Journal of Biological Chemistry"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.1016\/j.celrep.2017.11.031","article-title":"Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing","volume":"21","author":"Morris","year":"2017","journal-title":"Cell Reports"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.molcel.2016.11.018","article-title":"Autonomous Metabolic Oscillations Robustly Gate the Early and Late Cell Cycle","volume":"65","author":"Papagiannakis","year":"2017","journal-title":"Molecular Cell"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1038\/nchembio.2077","article-title":"Metabolite concentrations, fluxes and free energies imply efficient enzyme usage","volume":"12","author":"Park","year":"2016","journal-title":"Nature Chemical Biology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"5203","DOI":"10.1073\/pnas.090098797","article-title":"Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet beta cells","volume":"97","author":"Patterson","year":"2000","journal-title":"PNAS"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"98","DOI":"10.2144\/000113610","article-title":"Mitochondrial membrane potential probes and the proton gradient: a practical usage guide","volume":"50","author":"Perry","year":"2011","journal-title":"BioTechniques"},{"key":"bib50","doi-asserted-by":"publisher","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":"Molecular and Cellular Biochemistry"},{"key":"bib51","volume-title":"Metabolism at a Glance","author":"Salway","year":"2017"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085780","article-title":"Imaging mitochondrial flux in single cells with a FRET sensor for pyruvate","volume":"9","author":"San Mart\u00edn","year":"2014","journal-title":"PLOS ONE"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1016\/j.fertnstert.2018.07.022","article-title":"Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes","volume":"110","author":"Sanchez","year":"2018","journal-title":"Fertility and Sterility"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1093\/humrep\/dez210","article-title":"Combined noninvasive metabolic and spindle imaging as potential tools for embryo and oocyte assessment","volume":"34","author":"Sanchez","year":"2019","journal-title":"Human Reproduction"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23691-x","article-title":"Protein-bound NAD(P)H Lifetime is Sensitive to Multiple Fates of Glucose Carbon","volume":"8","author":"Sharick","year":"2018","journal-title":"Scientific Reports"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/s0962-8924(01)02246-2","article-title":"Mitochondrial dynamics and division in budding yeast","volume":"12","author":"Shaw","year":"2002","journal-title":"Trends in Cell Biology"},{"key":"bib57","doi-asserted-by":"publisher","DOI":"10.1117\/1.2717503","article-title":"In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia","volume":"12","author":"Skala","year":"2007","journal-title":"Journal of Biomedical Optics"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"3671","DOI":"10.1073\/pnas.88.9.3671","article-title":"Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1","volume":"88","author":"Smiley","year":"1991","journal-title":"PNAS"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1021\/ed069p981","article-title":"In vivo kinetics and the reversible Michaelis-Menten model","volume":"69","author":"Smith","year":"1992","journal-title":"Journal of Chemical Education"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/mben.1998.0101","article-title":"Metabolic fluxes and metabolic engineering","volume":"1","author":"Stephanopoulos","year":"1999","journal-title":"Metabolic Engineering"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/BF02578899","article-title":"A theoretical study on the amount of ATP required for synthesis of microbial cell material","volume":"39","author":"Stouthamer","year":"1973","journal-title":"Antonie van Leeuwenhoek"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s10815-013-0097-8","article-title":"A brief history of the development of the KSOM family of media","volume":"30","author":"Summers","year":"2013","journal-title":"Journal of Assisted Reproduction and Genetics"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.mib.2018.02.004","article-title":"Metabolic heterogeneity in clonal microbial populations","volume":"45","author":"Takhaveev","year":"2018","journal-title":"Current Opinion in Microbiology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.mito.2010.09.012","article-title":"Mitochondrial function in the human oocyte and embryo and their role in developmental competence","volume":"11","author":"Van Blerkom","year":"2011","journal-title":"Mitochondrion"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/nrc3365","article-title":"Mitochondria and cancer","volume":"12","author":"Wallace","year":"2012","journal-title":"Nature Reviews. Cancer"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.bbrc.2020.05.037","article-title":"Increase of mitochondria surrounding spindle causes mouse oocytes arrested at metaphase I stage","volume":"527","author":"Wang","year":"2020","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1002\/1097-0061(200011)16:15<1421::AID-YEA624>3.0.CO;2-U","article-title":"Mitochondria-targeted green fluorescent proteins: convenient tools for the study of organelle biogenesis in Saccharomyces cerevisiae","volume":"16","author":"Westermann","year":"2000","journal-title":"Yeast"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1006\/mben.2001.0187","article-title":"13C metabolic flux analysis","volume":"3","author":"Wiechert","year":"2001","journal-title":"Metabolic Engineering"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2026786118","article-title":"Physical bioenergetics: Energy fluxes, budgets, and constraints in cells","volume":"118","author":"Yang","year":"2021","journal-title":"PNAS"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1083\/jcb.201803152","article-title":"Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism","volume":"217","author":"Yellen","year":"2018","journal-title":"The Journal of Cell Biology"},{"key":"bib72","article-title":"FLIM-Interactive-Data-Analysis","volume-title":"GitHub","author":"Yoo","year":"2018","unstructured":"Yoo TY. 2018. FLIM-Interactive-Data-Analysis. GitHub. 38c432e. https:\/\/github.com\/taebong\/FLIM-Interactive-Data-Analysis\/tree\/v1.0.3."},{"key":"bib73","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1002\/jcp.22171","article-title":"Redistribution of mitochondria leads to bursts of ATP production during spontaneous mouse oocyte maturation","volume":"224","author":"Yu","year":"2010","journal-title":"Journal of Cellular Physiology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.cmet.2011.09.004","article-title":"Genetically encoded fluorescent sensors for intracellular NADH detection","volume":"14","author":"Zhao","year":"2011","journal-title":"Cell Metabolism"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/73808\/elife-73808-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/73808\/elife-73808-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/73808","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:23:30Z","timestamp":1697059410000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/73808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,22]]},"references-count":74,"alternative-id":["10.7554\/eLife.73808"],"URL":"https:\/\/doi.org\/10.7554\/elife.73808","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.11.20.392225","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2020.11.20.392225","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.73808.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.73808.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.73808.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,22]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e73808"}}