{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:33:58Z","timestamp":1791380038811,"version":"4.3.3"},"reference-count":285,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008239","name":"Highlands and Islands Enterprise","doi-asserted-by":"publisher","award":["HMS 9353763"],"award-info":[{"award-number":["HMS 9353763"]}],"id":[{"id":"10.13039\/100008239","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000723","name":"Tenovus","doi-asserted-by":"publisher","award":["G19.03"],"award-info":[{"award-number":["G19.03"]}],"id":[{"id":"10.13039\/501100000723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["A2819"],"award-info":[{"award-number":["A2819"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The consensus that assisted reproduction technologies (ART), like in vitro fertilization, to induce oxidative stress (i.e., the known) belies how oocyte\/zygote mitochondria\u2014a major presumptive oxidative stressor\u2014produce reactive oxygen species (ROS) with ART being unknown. Unravelling how oocyte\/zygote mitochondria produce ROS is important for disambiguating the molecular basis of ART-induced oxidative stress and, therefore, to rationally target it (e.g., using site-specific mitochondria-targeted antioxidants). I review the known mechanisms of ROS production in somatic mitochondria to critique how oocyte\/zygote mitochondria may produce ROS (i.e., the unknown). Several plausible site- and mode-defined mitochondrial ROS production mechanisms in ART are proposed. For example, complex I catalyzed reverse electron transfer-mediated ROS production is conceivable when oocytes are initially extracted due to at least a 10% increase in molecular dioxygen exposure (i.e., the intriguing). To address the term oxidative stress being used without recourse to the underlying chemistry, I use the species-specific spectrum of biologically feasible reactions to define plausible oxidative stress mechanisms in ART. Intriguingly, mitochondrial ROS-derived redox signals could regulate embryonic development (i.e., their production could be beneficial). Their potential beneficial role raises the clinical challenge of attenuating oxidative damage while simultaneously preserving redox signaling. This discourse sets the stage to unravel how mitochondria produce ROS in ART, and their biological roles from oxidative damage to redox signaling.<\/jats:p>","DOI":"10.3390\/antiox9100933","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T08:43:27Z","timestamp":1601369007000},"page":"933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing"],"prefix":"10.3390","volume":"9","author":[{"given":"James N.","family":"Cobley","sequence":"first","affiliation":[{"name":"Redox Biology Group, Institute for Health Sciences, University of the Highlands and Islands, Old Perth Road, Inverness IV2 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0926-6593(66)90057-9","article-title":"Antimycin-insensitive oxidation of succinate and reduced nicotinamide-adenine dinucleotide in electron-transport particles I. pH dependency and hydrogen peroxide formation","volume":"122","author":"Jensen","year":"1966","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/S0140-6736(78)92957-4","article-title":"Birth after the reimplantation of a human embryo","volume":"312","author":"Steptoe","year":"1978","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"O\u2019Flaherty, C. (2020). Reactive oxygen species and male fertility. Antioxidants, 9.","DOI":"10.3390\/antiox9040287"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sies, H. (1985). Oxidative Stress: Introductory Remarks. Oxidative Stress, Academic Press.","DOI":"10.1016\/B978-0-12-642760-8.50005-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1021\/ar00072a005","article-title":"How super is superoxide?","volume":"14","author":"Sawyer","year":"1981","journal-title":"Acc. Chem. Res."},{"key":"ref_6","unstructured":"Nicholls, D.G., and Ferguson, S.J. (2013). Bioenergetics 4, Academic Press. [4th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mailloux, R.J. (2020). An update on mitochondrial reactive oxygen species production. Antioxidants, 9.","DOI":"10.3390\/antiox9060472"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Halliwell, B., and Gutteridge, J.M.C. (2015). Free Radicals in Biology & Medicine, Oxford University Press. [5th ed.].","DOI":"10.1093\/acprof:oso\/9780198717478.001.0001"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/bies.950160105","article-title":"Radical solutions and cultural problems: Could free oxygen radicals be responsible for the impaired development of preimplantation mammalian embryos invitro?","volume":"16","author":"Johnson","year":"1994","journal-title":"BioEssays"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/humupd\/7.2.175","article-title":"Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings","volume":"7","author":"Guerin","year":"2001","journal-title":"Hum. Reprod. Update"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1089\/ars.2007.1964","article-title":"Redox considerations in female reproductive function and assisted reproduction: From molecular mechanisms to health implications","volume":"10","author":"Agarwal","year":"2008","journal-title":"Antioxid. Redox Sign."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1095\/biolreprod.112.106450","article-title":"Melatonin prevents postovulatory oocyte aging in the mouse and extends the window for optimal fertilization in vitro","volume":"88","author":"Lord","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R217","DOI":"10.1530\/REP-13-0111","article-title":"Oxidative stress and ageing of the post-ovulatory oocyte","volume":"146","author":"Lord","year":"2013","journal-title":"Reproduction"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.freeradbiomed.2019.08.002","article-title":"Coenzyme Q10 ameliorates the quality of postovulatory aged oocytes by suppressing DNA damage and apoptosis","volume":"143","author":"Zhang","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10130","DOI":"10.1038\/s41598-018-28497-5","article-title":"Mito-TEMPO improves development competence by reducing superoxide in preimplantation porcine embryos","volume":"8","author":"Yang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","first-page":"209","article-title":"Low oxygen concentrations for embryo culture in assisted reproductive technologies","volume":"19","author":"Bontekoe","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rampon, C., Volovitch, M., Joliot, A., and Vriz, S. (2018). Hydrogen Peroxide and Redox Regulation of Developments. Antioxidants, 7.","DOI":"10.20944\/preprints201809.0392.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: In sickness and in health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Aitken, R.J., and Drevet, J.R. (2020). The importance of oxidative stress in determining the functionality of mammalian spermatozoa: A two-edged sword. Antioxidants, 9.","DOI":"10.3390\/antiox9020111"},{"key":"ref_21","unstructured":"Lane, N. (2002). Oxygen: The Molecule that Made the World, Oxford University Press."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000339212","article-title":"Oxygen: How do we stand it?","volume":"22","author":"Fridovich","year":"2012","journal-title":"Med. Princ. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1038\/420027a","article-title":"Toxic oxygen: The radical life-giver","volume":"420","author":"Abele","year":"2002","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1039\/b926014p","article-title":"Singlet oxygen: There is indeed something new under the sun","volume":"39","author":"Ogilby","year":"2010","journal-title":"Chem. Soc. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1021\/cr1002003","article-title":"Proton-coupled electron transfer in cytochrome oxidase","volume":"110","author":"Kaila","year":"2010","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nchembio.85","article-title":"Reconciling the chemistry and biology of reactive oxygen species","volume":"4","author":"Winterbourn","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nchembio.607","article-title":"Chemistry and biology of reactive oxygen species in signaling or stress responses","volume":"7","author":"Dickinson","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1126\/science.210504","article-title":"The biology of oxygen radicals","volume":"201","author":"Fridovich","year":"1978","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative Stress","volume":"86","author":"Sies","year":"2017","journal-title":"Ann. Rev. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sies, H. (2020). Oxidative Stress: Concept and some Practical Aspects. Antioxidants, 9.","DOI":"10.3390\/antiox9090852"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sies, H. (2020). Oxidative Stress: Eustress and Distress, Academic Press.","DOI":"10.1016\/j.freeradbiomed.2020.12.032"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1089\/ars.2015.6247","article-title":"The Redox Code","volume":"23","author":"Jones","year":"2015","journal-title":"Antioxid. Redox Sign."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sies, H. (2020). How Exercise Induces Oxidative Eustress. Oxidative Stress, Elsevier.","DOI":"10.1016\/j.freeradbiomed.2020.12.032"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.redox.2015.01.002","article-title":"Oxidative stress: A concept in redox biology and medicine","volume":"4","author":"Sies","year":"2015","journal-title":"Redox Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2011.03.010","article-title":"Unraveling the biological roles of reactive oxygen species","volume":"13","author":"Murphy","year":"2011","journal-title":"Cell Metab."},{"key":"ref_36","first-page":"CD007176","article-title":"Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases","volume":"3","author":"Bjelakovic","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.bbabio.2006.04.015","article-title":"Electron tunneling chains of mitochondria","volume":"1757","author":"Moser","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1098\/rstb.2006.1868","article-title":"Darwin at the molecular scale: Selection and variance in electron tunnelling proteins including cytochrome c oxidase","volume":"361","author":"Moser","year":"2006","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1021\/cr500448t","article-title":"New perspectives on proton pumping in cellular respiration","volume":"115","author":"Sharma","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S0006-3495(66)86698-5","article-title":"Studies of photosynthesis using a pulsed laser: I. temperature dependence of cytochrome oxidation rate in chromatium. evidence for tunneling","volume":"6","author":"Chance","year":"1966","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nature11707","article-title":"Mitochondrial disorders as windows into an ancient organelle","volume":"491","author":"Vafai","year":"2012","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.redox.2015.02.001","article-title":"Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species","volume":"4","author":"Mailloux","year":"2015","journal-title":"Redox Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1126\/science.283.5407.1488","article-title":"Oxidative Phosphorylation at the fin de si\u00e8cle","volume":"283","author":"Saraste","year":"1999","journal-title":"Science"},{"key":"ref_44","first-page":"452","article-title":"Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism","volume":"192","author":"Mitchell","year":"1961","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20110773","article-title":"The ATP synthase: The understood, the uncertain and the unknown","volume":"41","author":"Walker","year":"2013","journal-title":"Biochem. Soc. Trans."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/35089509","article-title":"ATP synthase\u2014A marvellous rotary engine of the cell","volume":"2","author":"Yoshida","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2008","journal-title":"Biochem. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0304-4173(85)90014-X","article-title":"Electron transfers in chemistry and biology","volume":"811","author":"Marcus","year":"1985","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/355796a0","article-title":"Nature of biological electron transfer","volume":"355","author":"Moser","year":"1992","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.freeradbiomed.2019.01.048","article-title":"Evolutionary adaptations that enable enzymes to tolerate oxidative stress","volume":"140","author":"Imlay","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_51","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_52","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1152\/physrev.1979.59.3.527","article-title":"Hydroperoxide metabolism in mammalian organs","volume":"59","author":"Chance","year":"1979","journal-title":"Physiol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1042\/bj1340707","article-title":"The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen","volume":"134","author":"Boveris","year":"1973","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1089\/ars.2012.5148","article-title":"Updating the mitochondrial free radical theory of aging: An integrated view, key aspects, and confounding concepts","volume":"19","author":"Barja","year":"2013","journal-title":"Antioxid. Redox Sign."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1016\/S0021-9258(18)63504-5","article-title":"Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein)","volume":"244","author":"Mccord","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6176","DOI":"10.1016\/S0021-9258(18)62675-4","article-title":"Superoxide dismutase from escherichia coli B. A new manganese-containing enzyme","volume":"245","author":"Keele","year":"1970","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/0014-5793(74)80281-4","article-title":"Superoxide radicals as precursors of mitochondrial hydrogen peroxide","volume":"42","author":"Loschen","year":"1974","journal-title":"FEBS Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev-biochem-070511-103700","article-title":"Mitochondrial Complex I","volume":"82","author":"Hirst","year":"2013","journal-title":"Ann. Rev. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/nature13686","article-title":"Architecture of mammalian respiratory complex I","volume":"515","author":"Vinothkumar","year":"2014","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.bbabio.2011.04.006","article-title":"A two-state stabilization-change mechanism for proton-pumping complex I","volume":"1807","author":"Brandt","year":"2011","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kaila, V.R.I. (2018). Long-range proton-coupled electron transfer in biological energy conversion: Towards mechanistic understanding of respiratory complex I. J. R. Soc. Interface, 15.","DOI":"10.1098\/rsif.2017.0916"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.sbi.2020.01.004","article-title":"Respiratory complex I\u2014structure, mechanism and evolution","volume":"63","author":"Parey","year":"2020","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.1259859","article-title":"Mechanistic insight from the crystal structure of mitochondrial complex I","volume":"347","author":"Zickermann","year":"2015","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7607","DOI":"10.1073\/pnas.0510977103","article-title":"The mechanism of superoxide production by NADH: Ubiquinone oxidoreductase (complex I) from bovine heart mitochondria","volume":"103","author":"Kussmaul","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"18056","DOI":"10.1074\/jbc.M110.186841","article-title":"Superoxide is produced by the reduced flavin in mitochondrial complex I","volume":"286","author":"Pryde","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1042\/BJ20130606","article-title":"Investigating the function of [2Fe\u20132S] cluster N1a, the off-pathway cluster in complex I, by manipulating its reduction potential","volume":"456","author":"Birrell","year":"2013","journal-title":"Biochem. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1038\/s41467-019-10429-0","article-title":"A mechanism to prevent production of reactive oxygen species by Escherichia coli respiratory complex I","volume":"10","author":"Schulte","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2016.04.001","article-title":"Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling","volume":"100","author":"Brand","year":"2016","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.cmet.2015.12.009","article-title":"A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury","volume":"23","author":"Chouchani","year":"2016","journal-title":"Cell Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5169","DOI":"10.1016\/S0021-9258(18)99410-X","article-title":"Partial resolution of the enzymes catalyzing oxidative phosphorylation. XV. Reverse electron transfer in the flavin-cytochrome \u03b2 region of the respiratory chain of beef heart submitochondrial particles","volume":"242","author":"Hinkle","year":"1967","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nm.3212","article-title":"Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I","volume":"19","author":"Chouchani","year":"2013","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature13909","article-title":"Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS","volume":"515","author":"Chouchani","year":"2014","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s42255-019-0115-y","article-title":"Succinate accumulation drives ischaemia-reperfusion injury during organ transplantation","volume":"1","author":"Martin","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.cmet.2016.03.009","article-title":"Mitochondrial ROS produced via reverse electron transport extend animal lifespan","volume":"23","author":"Sriram","year":"2016","journal-title":"Cell Metab."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Onukwufor, J.O., Berry, B.J., and Wojtovich, A.P. (2019). Physiologic implications of reactive oxygen species production by mitochondrial complex I reverse electron transport. Antioxidants, 8.","DOI":"10.3390\/antiox8080285"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.cmet.2015.09.004","article-title":"Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex I signaling","volume":"22","author":"Gao","year":"2015","journal-title":"Cell Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cmet.2018.05.009","article-title":"Acute O2 sensing: Role of coenzyme QH2\/Q ratio and mitochondrial ROS compartmentalization","volume":"28","author":"Gao","year":"2018","journal-title":"Cell Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.celrep.2016.03.009","article-title":"The CoQH2\/CoQ ratio serves as a sensor of respiratory chain efficiency","volume":"15","author":"Calvo","year":"2016","journal-title":"Cell Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41586-019-1034-5","article-title":"A potassium channel \u03b2-subunit couples mitochondrial electron transport to sleep","volume":"568","author":"Kempf","year":"2019","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9869","DOI":"10.1074\/jbc.RA118.003647","article-title":"Control of mitochondrial superoxide production by reverse electron transport at complex I","volume":"293","author":"Robb","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1126\/science.1079605","article-title":"Architecture of succinate dehydrogenase and reactive oxygen species generation","volume":"299","author":"Yankovskaya","year":"2003","journal-title":"Science"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"27255","DOI":"10.1074\/jbc.M112.374629","article-title":"Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions","volume":"287","author":"Quinlan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.bbabio.2013.06.005","article-title":"Q-site inhibitor induced ROS production of mitochondrial complex II is attenuated by TCA cycle dicarboxylates","volume":"1827","author":"Siebels","year":"2013","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"42563","DOI":"10.1074\/jbc.M204958200","article-title":"Mechanism of superoxide and hydrogen peroxide formation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase","volume":"277","author":"Messner","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bbabio.2016.10.008","article-title":"Respiratory complex II: ROS production and the kinetics of ubiquinone reduction","volume":"1858","author":"Grivennikova","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Manhas, N., Duong, Q.V., Lee, P., Richardson, J.D., Robertson, J.D., Moxley, M.A., and Bazil, J.N. (2020). Computationally modeling mammalian succinate dehydrogenase kinetics identifies the origins and primary determinants of ROS production. J. Biol. Chem.","DOI":"10.1074\/jbc.RA120.014483"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0014-5793(75)80359-0","article-title":"The protonmotive Q cycle: A general formulation","volume":"59","author":"Mitchell","year":"1975","journal-title":"FEBS Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1146\/annurev.physiol.66.032102.150251","article-title":"The Cytochromebc1Complex: Function in the Context of Structure","volume":"66","author":"Crofts","year":"2004","journal-title":"Ann. Rev. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1042\/bj1560435","article-title":"Role of ubiquinone in the mitochondrial generation of hydrogen peroxide","volume":"156","author":"Boveris","year":"1976","journal-title":"Biochem. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-9861(77)90035-2","article-title":"Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria","volume":"180","author":"Cadenas","year":"1977","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.bbabio.2012.12.002","article-title":"Superoxide generation by complex III: From mechanistic rationales to functional consequences","volume":"1827","author":"Bleier","year":"2013","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_93","first-page":"227","article-title":"The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging","volume":"23","author":"Muller","year":"2000","journal-title":"J. Am. Aging Assoc."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"49064","DOI":"10.1074\/jbc.M407715200","article-title":"Complex III releases superoxide to both sides of the inner mitochondrial membrane","volume":"279","author":"Muller","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/104454902753759672","article-title":"HO2: The forgotten radical","volume":"21","year":"2002","journal-title":"DNA Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"44784","DOI":"10.1074\/jbc.M207217200","article-title":"Topology of superoxide production from different sites in the mitochondrial electron transport chain","volume":"277","author":"Buckingham","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1126\/science.1190899","article-title":"An electronic bus bar lies in the core of cytochrome bc1","volume":"329","author":"Cieluch","year":"2010","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"21649","DOI":"10.1074\/jbc.M803236200","article-title":"The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex","volume":"283","author":"Drose","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4759","DOI":"10.1016\/S0021-9258(18)32488-8","article-title":"A study of the reactivity of HO2\/O2-with unsaturated fatty acids","volume":"258","author":"Bielski","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_100","first-page":"1041","article-title":"Reactivity of HO2\/O2-radicals in aqueous solution","volume":"14","author":"Bielski","year":"1985","journal-title":"J. Phys. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"31361","DOI":"10.1074\/jbc.M111.267898","article-title":"The Mechanism of Superoxide Production by the Antimycin-inhibited Mitochondrial Q-cycle","volume":"286","author":"Quinlan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1042\/bj1880031","article-title":"Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria","volume":"188","author":"Cadenas","year":"1980","journal-title":"Biochem. J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"36027","DOI":"10.1074\/jbc.M304854200","article-title":"Production of reactive oxygen species by mitochondria","volume":"278","author":"Chen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.bbabio.2014.05.358","article-title":"Superoxide production by cytochrome bc1 complex: A mathematical model","volume":"1837","author":"Guillaud","year":"2014","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"101472","DOI":"10.1016\/j.redox.2020.101472","article-title":"Protein S-glutathionylation reactions as a global inhibitor of cell metabolism for the desensitization of hydrogen peroxide signals","volume":"32","author":"Mailloux","year":"2020","journal-title":"Redox Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"42921","DOI":"10.1074\/jbc.M112.397828","article-title":"A refined analysis of superoxide production by mitochondrialsn-glycerol 3-phosphate dehydrogenase","volume":"287","author":"Orr","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.freeradbiomed.2014.04.007","article-title":"Production of superoxide\/H2O2 by dihydroorotate dehydrogenase in rat skeletal muscle mitochondria","volume":"72","author":"Orr","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.freeradbiomed.2013.04.006","article-title":"Sites of superoxide and hydrogen peroxide production during fatty acid oxidation in rat skeletal muscle mitochondria","volume":"61","author":"Perevoshchikova","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1074\/jbc.M114.619072","article-title":"Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessedex vivounder conditions mimicking rest and exercise","volume":"290","author":"Quinlan","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.redox.2018.01.008","article-title":"13 reasons why the brain is susceptible to oxidative stress","volume":"15","author":"Cobley","year":"2018","journal-title":"Redox Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.redox.2018.03.012","article-title":"Mitochondrial ROS cause motor deficits induced by synaptic inactivity: Implications for synapse pruning","volume":"16","author":"Sidlauskaite","year":"2018","journal-title":"Redox Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e1800031","DOI":"10.1002\/bies.201800031","article-title":"Synapse pruning: Mitochondrial ROS with their hands on the shears","volume":"40","author":"Cobley","year":"2018","journal-title":"BioEssays"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/415096a","article-title":"Superoxide activates mitochondrial uncoupling proteins","volume":"415","author":"Echtay","year":"2002","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1016\/j.jmb.2018.03.025","article-title":"Use the protonmotive force: Mitochondrial uncoupling and reactive oxygen species","volume":"430","author":"Berry","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.freeradbiomed.2004.05.034","article-title":"Mitochondrial superoxide: Production, biological effects, and activation of uncoupling proteins","volume":"37","author":"Brand","year":"2004","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.str.2017.12.014","article-title":"Structure of the deactive state of mammalian respiratory complex I","volume":"26","author":"Blaza","year":"2018","journal-title":"Structure"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"20907","DOI":"10.1074\/jbc.M803190200","article-title":"Identification of the mitochondrial ND3 subunit as a structural component involved in the active\/deactive enzyme transition of respiratory complex I","volume":"283","author":"Galkin","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.bbabio.2014.02.018","article-title":"Characterisation of the active\/de-active transition of mitochondrial complex I","volume":"1837","author":"Babot","year":"2014","journal-title":"Biochim. Biophys. Acta-Bioenerg."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.bbabio.2015.12.013","article-title":"Ischemic A\/D transition of mitochondrial complex I and its role in ROS generation","volume":"1857","author":"Stepanova","year":"2016","journal-title":"Biochim. Biophys. Acta-Bioenerg."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/0012-1606(87)90395-2","article-title":"Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos","volume":"123","author":"Taylor","year":"1987","journal-title":"Dev. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/humupd\/dmu040","article-title":"IVF culture media: Past, present and future","volume":"21","author":"Chronopoulou","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.freeradbiomed.2017.10.003","article-title":"Limitations of oxygen delivery to cells in culture: An underappreciated problem in basic and translational research","volume":"113","author":"Place","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.fertnstert.2016.02.037","article-title":"Low versus atmospheric oxygen tension for embryo culture in assisted reproduction: A systematic review and meta-analysis","volume":"106","author":"Nastri","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1530\/jrf.0.0960219","article-title":"Effects of glucose, glutamine, ethylenediaminetetraacetic acid and oxygen tension on the concentration of reactive oxygen species and on development of the mouse preimplantation embryo in vitro","volume":"96","author":"Winston","year":"1992","journal-title":"J. Reprod. Fertil."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.semcdb.2008.12.013","article-title":"Mitochondrial function and redox state in mammalian embryos","volume":"20","author":"Dumollard","year":"2009","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.aad9642","article-title":"Hypoxia as a therapy for mitochondrial disease","volume":"352","author":"Jain","year":"2016","journal-title":"Science"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.rbmo.2019.03.102","article-title":"Individual culture and atmospheric oxygen during culture affect mouse preimplantation embryo metabolism and post-implantation development","volume":"39","author":"Kelley","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1021\/acs.chemrev.8b00554","article-title":"Singlet molecular oxygen reactions with nucleic acids, lipids, and proteins","volume":"119","author":"Martinez","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"14289","DOI":"10.1073\/pnas.0706687104","article-title":"Effects of light on development of mammalian zygotes","volume":"104","author":"Takenaka","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"6255","DOI":"10.1073\/pnas.96.11.6255","article-title":"Activation of flavin-containing oxidases underlies light-induced production of H2O2 in mammalian cells","volume":"96","author":"Hockberger","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"15038","DOI":"10.1073\/pnas.0601945103","article-title":"Selective fluorescent imaging of superoxide in vivo using ethidium-based probes","volume":"103","author":"Robinson","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2011.09.030","article-title":"Measuring reactive oxygen and nitrogen species with fluorescent probes: Challenges and limitations","volume":"52","author":"Kalyanaraman","year":"2011","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.exger.2010.01.003","article-title":"The sites and topology of mitochondrial superoxide production","volume":"45","author":"Brand","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1242\/dev.113.2.551","article-title":"The origin of reactive oxygen species in mouse embryos cultured in vitro","volume":"113","author":"Johnson","year":"1991","journal-title":"Development"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.freeradbiomed.2005.10.042","article-title":"The oxidation of 2\u2032,7\u2032-dichlorofluorescin to reactive oxygen species: A self-fulfilling prophesy?","volume":"40","author":"Bonini","year":"2006","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.freeradbiomed.2007.06.026","article-title":"Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: Progress, pitfalls, and prospects","volume":"43","author":"Wardman","year":"2007","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.freeradbiomed.2018.03.032","article-title":"Small-molecule luminescent probes for the detection of cellular oxidizing and nitrating species","volume":"128","author":"Zielonka","year":"2018","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_138","doi-asserted-by":"crossref","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","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/humrep\/17.2.393","article-title":"Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos","volume":"17","author":"Davis","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1093\/humrep\/16.5.909","article-title":"Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos","volume":"16","author":"Wilding","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S1472-6483(10)60622-0","article-title":"High-polarized (\u0394\u03a8mHIGH) mitochondria are spatially polarized in human oocytes and early embryos in stable subplasmalemmal domains: Developmental significance and the concept of vanguard mitochondria","volume":"13","author":"Davis","year":"2006","journal-title":"Reprod. Biomed. Online"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/molehr\/gam068","article-title":"Mitochondrial signaling and fertilization","volume":"13","author":"Davis","year":"2007","journal-title":"Mol. Hum. Reprod."},{"key":"ref_143","doi-asserted-by":"crossref","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":"Curr. Top. Dev. Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1016\/j.mito.2007.04.002","article-title":"Analysis of coenzyme Q in human blood and tissues","volume":"7","author":"Barshop","year":"2007","journal-title":"Mitochondrion"},{"key":"ref_145","doi-asserted-by":"crossref","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":"ref_146","doi-asserted-by":"crossref","first-page":"7631","DOI":"10.1073\/pnas.95.13.7631","article-title":"Persistent inhibition of cell respiration by nitric oxide: Crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione","volume":"95","author":"Clementi","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1021\/tx300042g","article-title":"Connecting the chemical and biological properties of nitric oxide","volume":"25","author":"Toledo","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/molehr\/gan037","article-title":"Regulation of mitochondrial polarity in mouse and human oocytes: The influence of cumulus derived nitric oxide","volume":"14","author":"Davis","year":"2008","journal-title":"Mol. Hum. Reprod."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.bbabio.2013.01.004","article-title":"Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning","volume":"1827","year":"2013","journal-title":"Biochim. Biophys. Acta-Bioenerg."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nchembio.1910","article-title":"Suppressors of superoxide production from mitochondrial complex III","volume":"11","author":"Orr","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.cmet.2016.08.012","article-title":"Suppressors of superoxide-H2O2 production at site I Q of mitochondrial complex i protect against stem cell hyperplasia and ischemia-reperfusion injury","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.freeradbiomed.2019.09.006","article-title":"S1QELs suppress mitochondrial superoxide\/hydrogen peroxide production from site IQ without inhibiting reverse electron flow through Complex I","volume":"143","author":"Wong","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"101341","DOI":"10.1016\/j.redox.2019.101341","article-title":"The use of site-specific suppressors to measure the relative contributions of different mitochondrial sites to skeletal muscle superoxide and hydrogen peroxide production","volume":"28","author":"Goncalves","year":"2020","journal-title":"Redox Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"6550","DOI":"10.1074\/jbc.RA119.007687","article-title":"Defining the mechanism of action of S1QELs, specific suppressors of superoxide production in the quinone-reaction site in mitochondrial complex I","volume":"294","author":"Banba","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.freeradbiomed.2016.02.005","article-title":"Going retro: Oxidative stress biomarkers in modern redox biology","volume":"98","author":"Margaritelis","year":"2016","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cellsig.2015.12.011","article-title":"Principles for integrating reactive species into in vivo biological processes: Examples from exercise physiology","volume":"28","author":"Margaritelis","year":"2016","journal-title":"Cell. Sign."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"21295","DOI":"10.1074\/jbc.M501527200","article-title":"Interactions of Mitochondria-targeted and Untargeted Ubiquinones with the mitochondrial respiratory chain and reactive oxygen species","volume":"280","author":"James","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.freeradbiomed.2013.04.010","article-title":"Antioxidants as therapies: Can we improve on nature?","volume":"66","author":"Murphy","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.freeradbiomed.2015.07.160","article-title":"A mitochondria-targeted derivative of ascorbate: MitoC","volume":"89","author":"Finichiu","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.1749-6632.2010.05627.x","article-title":"Animal and human studies with the mitochondria-targeted antioxidant MitoQ","volume":"1201","author":"Smith","year":"2010","journal-title":"Ann. N. Y. Acad. Sci. USA"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1089\/ars.2011.3969","article-title":"Mitochondria-targeted small molecule therapeutics and probes","volume":"15","author":"Smith","year":"2011","journal-title":"Antioxid. Redox Sign."},{"key":"ref_162","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","volume":"276","author":"Kelso","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1046\/j.1432-1327.1999.00543.x","article-title":"Selective targeting of an antioxidant to mitochondria","volume":"263","author":"Smith","year":"1999","journal-title":"Eur. J. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1089\/ars.2009.2876","article-title":"superoxide dismutase mimics: Chemistry, pharmacology, and therapeutic potential","volume":"13","author":"Spasojevic","year":"2010","journal-title":"Antioxid. Redox Sign."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1089\/ars.2012.5147","article-title":"SOD therapeutics: Latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways","volume":"20","author":"Tovmasyan","year":"2014","journal-title":"Antioxid. Redox Sign."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.redox.2015.01.017","article-title":"An educational overview of the chemistry, biochemistry and therapeutic aspects of Mn porphyrins\u2013From superoxide dismutation to H2O2-driven pathways","volume":"5","author":"Tovmasyan","year":"2015","journal-title":"Redox Biol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.bbrc.2010.02.071","article-title":"Antioxidants: Molecules, medicines, and myths","volume":"393","author":"Gutteridge","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1016\/j.febslet.2012.09.025","article-title":"Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products?","volume":"586","author":"Niki","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.freeradbiomed.2013.03.022","article-title":"Role of vitamin E as a lipid-soluble peroxyl radical scavenger: In vitro and in vivo evidence","volume":"66","author":"Niki","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1089\/ars.2009.2948","article-title":"Fluorescent Protein-Based Redox Probes","volume":"13","author":"Meyer","year":"2010","journal-title":"Antioxid. Redox Sign."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.cmet.2011.02.003","article-title":"Measurement of H2O2 within living drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix","volume":"13","author":"Quin","year":"2011","journal-title":"Cell Metab."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.bbagen.2013.05.026","article-title":"Using exomarkers to assess mitochondrial reactive species in vivo","volume":"1840","author":"Logan","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/j.chembiol.2017.08.003","article-title":"MitoNeoD: A mitochondria-targeted superoxide probe","volume":"24","author":"Shchepinova","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.freeradbiomed.2010.01.028","article-title":"Hydroethidine- and MitoSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: Another inconvenient truth","volume":"48","author":"Zielonka","year":"2010","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1089\/ars.2019.7725","article-title":"Redox Systems Biology: Harnessing the Sentinels of the Cysteine Redoxome","volume":"32","author":"Held","year":"2020","journal-title":"Antioxid. Redox Sign."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2020.02.012","article-title":"A Quantitative tissue-specific landscape of protein redox regulation during aging","volume":"180","author":"Xiao","year":"2020","journal-title":"Cell"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.freeradbiomed.2018.09.012","article-title":"Proteomic strategies to unravel age-related redox signalling defects in skeletal muscle","volume":"132","author":"Cobley","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/mcp.O115.056051","article-title":"The expanding landscape of the thiol redox proteome","volume":"15","author":"Yang","year":"2015","journal-title":"Mol. Cell. Proteom."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.chembiol.2015.06.010","article-title":"Site-specific proteomic mapping identifies selectively modified regulatory cysteine residues in functionally distinct protein networks","volume":"22","author":"Gould","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.vascn.2013.07.001","article-title":"The PEG-switch assay: A fast semi-quantitative method to determine protein reversible cysteine oxidation","volume":"68","author":"Burgoyne","year":"2013","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.freeradbiomed.2017.03.037","article-title":"Click-PEGylation - A mobility shift approach to assess the redox state of cysteines in candidate proteins","volume":"108","author":"Hinchy","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"101258","DOI":"10.1016\/j.redox.2019.101258","article-title":"Catalyst-free Click PEGylation reveals substantial mitochondrial ATP synthase sub-unit alpha oxidation before and after fertilisation","volume":"26","author":"Cobley","year":"2019","journal-title":"Redox Biol."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Cobley, J.N., and Husi, H. (2020). Immunological techniques to assess protein thiol redox state: Opportunities, challenges and solutions. Antioxidants, 9.","DOI":"10.3390\/antiox9040315"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cmet.2015.11.014","article-title":"Assessing the mitochondrial membrane potential in cells and in vivo using targeted click chemistry and mass spectrometry","volume":"23","author":"Logan","year":"2016","journal-title":"Cell Metab."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.freeradbiomed.2019.11.028","article-title":"A sensitive mass spectrometric assay for mitochondrial CoQ pool redox state in vivo","volume":"147","author":"Burger","year":"2020","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.freeradbiomed.2015.08.021","article-title":"Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat","volume":"89","author":"Robb","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.chembiol.2018.12.002","article-title":"Selective disruption of mitochondrial thiol redox state in cells and in vivo","volume":"26","author":"Booty","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1038\/nprot.2013.095","article-title":"Analysis of GSH and GSSG after derivatization with N-ethylmaleimide","volume":"8","author":"Giustarini","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nprot.2009.197","article-title":"Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue","volume":"5","author":"Weydert","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.semcdb.2006.02.009","article-title":"Calcium signals and mitochondria at fertilisation","volume":"17","author":"Dumollard","year":"2006","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Muller, B., Lewis, N., Adeniyi, T., Leese, H.J., Brison, D.R., and Sturmey, R.G. (2019). Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-53066-9"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/oxfordjournals.humrep.a135954","article-title":"Fertilization and early embryolgoy: ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer","volume":"10","author":"Davis","year":"1995","journal-title":"Hum. Reprod."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1006\/jtbi.1996.0089","article-title":"Separate Sexes and the Mitochondrial Theory of Ageing","volume":"180","author":"Allen","year":"1996","journal-title":"J. Theor. Biol."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Hernansanz-Agust\u00edn, P., Choya-Foces, C., Carregal-Romero, S., Ramos, E., Oliva, T., Villa-Pi\u00f1a, T., Moreno, L., Izquierdo-\u00c1lvarez, A., Cabrera-Garc\u00eda, J.D., and Cort\u00e9s, A. (2020). Na+ controls hypoxic signalling by the mitochondrial respiratory chain. Nature.","DOI":"10.1038\/s41586-020-2551-y"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1073\/pnas.58.2.560","article-title":"The pattern of energy metabolism in the mouse oocyte and zygote","volume":"58","author":"Biggers","year":"1967","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_196","doi-asserted-by":"crossref","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":"485","author":"Houghton","year":"1996","journal-title":"Mol. Reprod. Dev."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.freeradbiomed.2017.02.046","article-title":"Protein S-glutathionylation alters superoxide\/hydrogen peroxide emission from pyruvate dehydrogenase complex","volume":"106","author":"Chalker","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0192801","article-title":"Protein S-glutathionylation lowers superoxide\/hydrogen peroxide release from skeletal muscle mitochondria through modification of complex I and inhibition of pyruvate uptake","volume":"13","author":"Gill","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"18361","DOI":"10.1074\/jbc.M500174200","article-title":"Mitochondrial malate-aspartate shuttle regulates mouse embryo nutrient consumption","volume":"280","author":"Lane","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cell.2016.12.026","article-title":"Nuclear localization of mitochondrial TCA cycle enzymes as a critical step in mammalian zygotic genome activation","volume":"168","author":"Nagaraj","year":"2017","journal-title":"Cell"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.cmet.2018.01.008","article-title":"Metabolism in pluripotent stem cells and early mammalian development","volume":"27","author":"Zhang","year":"2018","journal-title":"Cell Metab."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1530\/rep.0.1260197","article-title":"Energy metabolism in pig oocytes and early embryos","volume":"126","author":"Sturmey","year":"2003","journal-title":"Reproduction"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/humrep\/15.suppl_2.129","article-title":"Mitochondrial morphology in human fetal and adult female germ cells","volume":"15","author":"Motta","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"E7978","DOI":"10.1073\/pnas.1807918115","article-title":"Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes","volume":"115","author":"Petrova","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1042\/BST20120352","article-title":"Parallels between embryo and cancer cell metabolism","volume":"41","author":"Smith","year":"2013","journal-title":"Biochem. Soc. Trans."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"7740","DOI":"10.1073\/pnas.0910410107","article-title":"Bovine cytochromecoxidase structures enable O2 reduction with minimization of reactive oxygens and provide a proton-pumping gate","volume":"107","author":"Muramoto","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_207","first-page":"63","article-title":"Oxygen radicals, a failure or sucess of evolution","volume":"18","author":"Barja","year":"1993","journal-title":"Free Radic. Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2174\/187152011795677544","article-title":"Superoxide dismutase in redox biology: The roles of superoxide and hydrogen peroxide","volume":"11","author":"Buettner","year":"2011","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_209","unstructured":"Lane, N. (2015). The Vital Question: Energy, Evolution, and the Origins of Complex Life, Profile Books Limited."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1074\/jbc.R111.271999","article-title":"Signal transduction by mitochondrial oxidants","volume":"287","author":"Finkel","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"10231","DOI":"10.1073\/pnas.1500012112","article-title":"Why chloroplasts and mitochondria retain their own genomes and genetic systems: Colocation for redox regulation of gene expression","volume":"112","author":"Allen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1530\/REP-09-0430","article-title":"Short-term exposure to hydrogen peroxide during oocyte maturation improves bovine embryo development","volume":"139","author":"Vandaele","year":"2010","journal-title":"Reproduction"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.freeradbiomed.2006.07.015","article-title":"A new paradigm: Manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state","volume":"41","author":"Buettner","year":"2006","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0005-2728(99)00025-0","article-title":"Nitric oxide and mitochondrial respiration","volume":"1411","author":"Brown","year":"1999","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"14064","DOI":"10.1074\/jbc.275.19.14064","article-title":"Mitochondrial Aconitase Is a Source of Hydroxyl Radical","volume":"275","author":"Kalyanaraman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"19328","DOI":"10.1016\/S0021-9258(18)55001-8","article-title":"Superoxide sensitivity of the Escherichia coli aconitase","volume":"266","author":"Gardner","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.bbapap.2009.11.005","article-title":"Superoxide dismutases\u2014A review of the metal-associated mechanistic variations","volume":"1804","author":"Abreu","year":"2010","journal-title":"Biochim. Biophys. Acta-Proteins Proteom."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1021\/cr4005296","article-title":"Superoxide Dismutases and Superoxide Reductases","volume":"114","author":"Sheng","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40828-019-0101-8","article-title":"Biological chemistry of superoxide radicals","volume":"6","author":"Winterbourn","year":"2020","journal-title":"ChemTexts"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nrmicro3032","article-title":"The molecular mechanisms and physiological consequences of oxidative stress: Lessons from a model bacterium","volume":"11","author":"Imlay","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.chembiol.2018.01.007","article-title":"Switch of mitochondrial superoxide dismutase into a prooxidant peroxidase in manganese-deficient cells and mice","volume":"25","author":"Ganini","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1089\/ars.2019.7962","article-title":"Mitochondrial superoxide dismutase: What the established, the intriguing, and the novel reveal about a key cellular redox switch","volume":"32","author":"Palma","year":"2020","journal-title":"Antioxid. Redox Sign."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.bbrc.2012.05.055","article-title":"Complex I generated, mitochondrial matrix-directed superoxide is released from the mitochondria through voltage dependent anion channels","volume":"422","author":"Lustgarten","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1073\/pnas.87.4.1620","article-title":"Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide","volume":"87","author":"Beckman","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"26464","DOI":"10.1074\/jbc.R113.472936","article-title":"Peroxynitrite, a stealthy biological oxidant","volume":"288","author":"Radi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.bbagen.2013.07.005","article-title":"Kinetic and mechanistic considerations to assess the biological fate of peroxynitrite","volume":"1840","author":"Carballal","year":"2014","journal-title":"Biochim. Biophys. Acta-Gen. Subj."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1042\/BJ20091541","article-title":"Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling","volume":"425","author":"Cox","year":"2010","journal-title":"Biochem. J."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1089\/ars.2011.4289","article-title":"Mitochondrial thiols in antioxidant protection and redox signaling: Distinct roles for glutathionylation and other thiol modifications","volume":"16","author":"Murphy","year":"2012","journal-title":"Antioxid. Redox Sign."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Smith, C.D., Schmidt, C.A., Lin, C.-T., Fisher-Wellman, K.H., and Neufer, P. (2020). Flux through mitochondrial redox circuits linked to nicotinamide nucleotide transhydrogenase generates counterbalance changes in energy expenditure. J. Biol. Chem.","DOI":"10.1074\/jbc.RA120.013899"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nchembio.1695","article-title":"Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling","volume":"11","author":"Sobotta","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.cmet.2020.02.003","article-title":"Ultrasensitive genetically encoded indicator for hydrogen peroxide identifies roles for the oxidant in cell migration and mitochondrial function","volume":"31","author":"Pak","year":"2020","journal-title":"Cell Metab."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1089\/ars.2017.7425","article-title":"Biological Production, Detection, and Fate of Hydrogen Peroxide","volume":"20","author":"Winterbourn","year":"2018","journal-title":"Antioxid. Redox Sign."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1042\/BST0351147","article-title":"Biochemistry of oxidative stress","volume":"35","author":"Sies","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"16330","DOI":"10.1016\/S0021-9258(17)46227-2","article-title":"The oxidative inactivation of mitochondrial electron transport chain components and ATPase","volume":"265","author":"Zhang","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0070-2153(06)77004-1","article-title":"Mitochondrial DNA and the mammalian oocyte","volume":"77","author":"Shoubridge","year":"2007","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/2046-2395-2-11","article-title":"Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle","volume":"2","author":"Cobley","year":"2013","journal-title":"Longev. Health"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphys.2015.00182","article-title":"The basic chemistry of exercise-induced DNA oxidation: Oxidative damage, redox signaling, and their interplay","volume":"6","author":"Cobley","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"101673","DOI":"10.1016\/j.redox.2020.101673","article-title":"The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage","volume":"36","author":"Williamson","year":"2020","journal-title":"Redox Biol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/bies.201100051","article-title":"Mitonuclear match: Optimizing fitness and fertility over generations drives ageing within generations","volume":"33","author":"Lane","year":"2011","journal-title":"BioEssays"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nature18618","article-title":"Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing","volume":"535","author":"Torroja","year":"2016","journal-title":"Nature"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1021\/cr300163e","article-title":"Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery","volume":"113","author":"Paulsen","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"8798","DOI":"10.1021\/acs.chemrev.7b00698","article-title":"Redox signaling by reactive electrophiles and oxidants","volume":"118","author":"Parvez","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2008.03.011","article-title":"Redox-based regulation of signal transduction: Principles, pitfalls, and promises","volume":"45","author":"Mossman","year":"2008","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.freeradbiomed.2015.03.018","article-title":"Influence of vitamin C and vitamin E on redox signaling: Implications for exercise adaptations","volume":"84","author":"Cobley","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nchembio.2412","article-title":"A scaffold protein that chaperones a cysteine-sulfenic acid in H2O2 signaling","volume":"13","author":"Bersweiler","year":"2017","journal-title":"Nat. Chem. Rev. Biol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.redox.2016.12.035","article-title":"Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress","volume":"11","author":"Sies","year":"2017","journal-title":"Redox Biol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.freeradbiomed.2015.03.022","article-title":"The cysteine proteome","volume":"84","author":"Go","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1242\/jcs.110486","article-title":"Mitochondrial redox signalling at a glance","volume":"125","author":"Collins","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/j.1742-4658.2010.07576.x","article-title":"Cysteine residues exposed on protein surfaces are the dominant intramitochondrial thiol and may protect against oxidative damage","volume":"277","author":"Requejo","year":"2010","journal-title":"FEBS J."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.bbapap.2014.02.006","article-title":"Mitochondrial respiratory chain complexes as sources and targets of thiol-based redox-regulation","volume":"1844","author":"Brandt","year":"2014","journal-title":"Biochim. Biophys. Acta-Proteins Proteom."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"24801","DOI":"10.1074\/jbc.M803432200","article-title":"Complex I within oxidatively stressed bovine heart mitochondria is glutathionylated on Cys-531 and Cys-704 of the 75-kDa subunit","volume":"283","author":"Hurd","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1161\/CIRCRESAHA.111.246124","article-title":"Redox regulation of mitochondrial ATP synthase: Implications for cardiac resynchronization therapy","volume":"109","author":"Wang","year":"2011","journal-title":"Circ. Res."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.tcm.2012.08.005","article-title":"Redox regulation of mitochondrial ATP synthase","volume":"23","author":"Wang","year":"2013","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Cobley, J.N., Noble, A., Bessell, R., Guille, M., and Husi, H. (2020). Reversible thiol oxidation inhibits the mitochondrial ATP Synthase in Xenopus laevis Oocytes. Antioxidants, 9.","DOI":"10.3390\/antiox9030215"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/humupd\/dmp016","article-title":"Mitochondrial functionality in reproduction: From gonads and gametes to embryos and embryonic stem cells","volume":"15","author":"Varum","year":"2009","journal-title":"Hum. Reprod. Update"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.freeradbiomed.2008.05.004","article-title":"Thiol chemistry and specificity in redox signaling","volume":"45","author":"Winterbourn","year":"2008","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1089\/ars.2010.3534","article-title":"Basic principles and emerging concepts in the redox control of transcription factors","volume":"15","year":"2011","journal-title":"Antioxid. Redox Sign."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1089\/ars.2017.7162","article-title":"The conundrum of hydrogen peroxide signaling and the emerging role of peroxiredoxins as redox relay hubs","volume":"28","author":"Mijuskovic","year":"2018","journal-title":"Antioxid. Redox Sign."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cell.2010.01.009","article-title":"Inactivation of peroxiredoxin i by phosphorylation allows localized H2O2 accumulation for cell signaling","volume":"140","author":"Woo","year":"2010","journal-title":"Cell"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ceb.2014.09.010","article-title":"ROS-dependent signal transduction","volume":"33","author":"Reczek","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.redox.2017.03.022","article-title":"Exercise redox biochemistry: Conceptual, methodological and technical recommendations","volume":"12","author":"Cobley","year":"2017","journal-title":"Redox Biol."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20190049","article-title":"Hydrogen peroxide reactivity and specificity in thiol-based cell signalling","volume":"48","author":"Winterbourn","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"12330","DOI":"10.1074\/jbc.RA119.009001","article-title":"Bicarbonate is essential for protein-tyrosine phosphatase 1B (PTP1B) oxidation and cellular signaling through EGF-triggered phosphorylation cascades","volume":"294","author":"Dagnell","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0891-5849(02)00786-4","article-title":"Nitrogen dioxide and carbonate radical anion: Two emerging radicals in biology","volume":"32","author":"Augusto","year":"2002","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.abb.2015.11.028","article-title":"Revisiting the reactions of superoxide with glutathione and other thiols","volume":"595","author":"Winterbourn","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0891-5849(93)90512-S","article-title":"Superoxide as an intracellular radical sink","volume":"14","author":"Winterbourn","year":"1993","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.freeradbiomed.2014.08.017","article-title":"Are free radicals involved in thiol-based redox signaling?","volume":"80","author":"Winterbourn","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.freeradbiomed.2012.05.025","article-title":"Protein thiyl radical mediates S-glutathionylation of complex I","volume":"53","author":"Kang","year":"2012","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1095\/biolreprod62.6.1866","article-title":"Oxidative phosphorylation-dependent and -independent oxygen consumption by individual preimplantation mouse embryos1","volume":"62","author":"Trimarchi","year":"2000","journal-title":"Biol. Reprod."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1242\/dev.109.2.501","article-title":"Hydrogen peroxide levels in mouse oocytes and early cleavage stage embryos developed in vitro or in vivo","volume":"109","author":"Aitken","year":"1990","journal-title":"Development"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1073\/pnas.75.7.3183","article-title":"Hydrogen peroxide production, chemiluminescence, and the respiratory burst of fertilization: Interrelated events in early sea urchin development","volume":"75","author":"Foerder","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1073\/pnas.86.4.1259","article-title":"Respiratory burst oxidase of fertilization","volume":"86","author":"Heinecke","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.devcel.2004.10.014","article-title":"The oxidative burst at fertilization is dependent upon activation of the dual oxidase Udx1","volume":"7","author":"Wong","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.celrep.2017.12.042","article-title":"Ca 2+ Induced mitochondrial ros regulate the early embryonic cell cycle","volume":"22","author":"Han","year":"2018","journal-title":"Cell Rep."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1530\/jrf.0.0950649","article-title":"Release of two-cell block by reduction of protein disulfide with thioredoxin from Escherichia coli in mice","volume":"95","author":"Natsuyama","year":"1992","journal-title":"J. Reprod. Fertil."},{"key":"ref_276","first-page":"90","article-title":"Superoxide dismutase and thioredoxin restore defective p34cdc2 kinase activation in mouse two-cell block","volume":"1176","author":"Natsuyama","year":"1993","journal-title":"BBA-Mol. Cell Res."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1089\/ars.2009.3044","article-title":"Redox control in mammalian embryo development","volume":"13","author":"Ufer","year":"2010","journal-title":"Antioxid. Redox Sign."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.freeradbiomed.2016.04.025","article-title":"Oncometabolites: Unconventional triggers of oncogenic signalling cascades","volume":"100","author":"Sciacovelli","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s42255-018-0014-7","article-title":"Coupling Krebs cycle metabolites to signalling in immunity and cancer","volume":"1","author":"Ryan","year":"2018","journal-title":"Nat. Metab."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"R159","DOI":"10.1530\/REP-18-0431","article-title":"Mitochondria in early development: Linking the microenvironment, metabolism and the epigenome","volume":"157","author":"Harvey","year":"2019","journal-title":"Reproduction"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.freeradbiomed.2007.06.027","article-title":"An epigenetic perspective on the free radical theory of development","volume":"43","author":"Hitchler","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41586-019-1814-y","article-title":"Developmental ROS individualizes organismal stress resistance and lifespan","volume":"576","author":"Bazopoulou","year":"2019","journal-title":"Nature"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.molcel.2012.06.016","article-title":"Quantitative in vivo redox sensors uncover oxidative stress as an early event in life","volume":"47","author":"Knoefler","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_284","doi-asserted-by":"crossref","unstructured":"Lozoya, O.A., Xu, F., Grenet, D., Wang, T., Grimm, S.A., Godfrey, V., Waidyanatha, S., Woychik, R.P., and Santos, J.H. (2020). Single nucleotide resolution analysis reveals pervasive, long-lasting DNA methylation changes by developmental exposure to a mitochondrial toxicant. Cell Rep., 32.","DOI":"10.1016\/j.celrep.2020.108131"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"101606","DOI":"10.1016\/j.redox.2020.101606","article-title":"Mitochondria-targeted paraquat and metformin mediate ROS production to induce multiple pathways of retrograde signaling: A dose-dependent phenomenon","volume":"36","author":"Chowdhury","year":"2020","journal-title":"Redox Biol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/10\/933\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:14:44Z","timestamp":1760177684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/10\/933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,29]]},"references-count":285,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["antiox9100933"],"URL":"https:\/\/doi.org\/10.3390\/antiox9100933","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,29]]}}}