biostudies-literatureYoval-Sanchez BAmerican Heart AssociationBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftNHLBI NIH HHSNINDS NIH HHSNational Institutes of HealthNIH HHS102258https://www.ebi.ac.uk/biostudies/studies/S-EPMC8861397biostudies-literatureUnknown51Pathologies associated with tissue ischemia/reperfusion (I/R) in highly metabolizing organs such as the brain and heart are leading causes of death and disability in humans. Molecular mechanisms underlying mitochondrial dysfunction during acute injury in I/R are tissue-specific, but their details are not completely understood. A metabolic shift and accumulation of substrates of reverse electron transfer (RET) such as succinate are observed in tissue ischemia, making mitochondrial complex I of the respiratory chain (NADH:ubiquinone oxidoreductase) the most vulnerable enzyme to the following reperfusion. It has been shown that brain complex I is predisposed to losing its flavin mononucleotide (FMN) cofactor when maintained in the reduced state in conditions of RET both in vitro and in vivo. Redox biologyRedox-dependent loss of flavin by mitochondria complex I is different in brain and heart.PMC8861397SFB815/Z1834220R01 NS112381R01HL132918R01 HL132918R01 HL151447R01 NS100850R01HL151447NS100850RO1NS112381S10 OD030335Sosunov SWittig IYoval-Sanchez BTikhonova IGAnsari FFilipenko PJames JTen VRafikov RNiatsetskaya ZGalkin AfalseRedox-dependent loss of flavin by mitochondria complex I is different in brain and heart.Pathologies associated with tissue ischemia/reperfusion (I/R) in highly metabolizing organs such as the brain and heart are leading causes of death and disability in humans. Molecular mechanisms underlying mitochondrial dysfunction during acute injury in I/R are tissue-specific, but their details are not completely understood. A metabolic shift and accumulation of substrates of reverse electron transfer (RET) such as succinate are observed in tissue ischemia, making mitochondrial complex I of the respiratory chain (NADH:ubiquinone oxidoreductase) the most vulnerable enzyme to the following reperfusion. It has been shown that brain complex I is predisposed to losing its flavin mononucleotide (FMN) cofactor when maintained in the reduced state in conditions of RET both in vitro and in vivo. 2022-01-01T00:00:00Z2022 May2026-04-08T08:25:16.516Z2025-02-19T03:26:18.909ZS-EPMC88613973518955010.1016/j.redox.2022.102258