biostudies-literatureUnknown63Semenzato MDuring cardiac ischemia-reperfusion, excess reactive oxygen species can damage mitochondrial, cellular and organ function. Here we show that cysteine oxidation of the mitochondrial protein Opa1 contributes to mitochondrial damage and cell death caused by oxidative stress. Oxy-proteomics of ischemic-reperfused hearts reveal oxidation of the C-terminal C786 of Opa1 and treatment of perfused mouse hearts, adult cardiomyocytes, and fibroblasts with H₂O₂ leads to the formation of a reduction-sensitive ∼180 KDa Opa1 complex, distinct from the ∼270 KDa one antagonizing cristae remodeling. This Opa1 oxidation process is curtailed by mutation of C786 and of the other 3 Cys residues of its C-terminal domain (Opa1^TetraCys). When reintroduced in Opa1^-/- cellRedox biology102755https://www.ebi.ac.uk/biostudies/studies/S-EPMC10220262biostudies-literatureOxidization of optic atrophy 1 cysteines occurs during heart ischemia-reperfusion and amplifies cell death by oxidative stress.PMC10220262Semenzato MMenabo RAlanova PDi Lisa FKohr MJQuirin CMurphy EPellattiero AScorrano LAlan LfalseOxidization of optic atrophy 1 cysteines occurs during heart ischemia-reperfusion and amplifies cell death by oxidative stress.During cardiac ischemia-reperfusion, excess reactive oxygen species can damage mitochondrial, cellular and organ function. Here we show that cysteine oxidation of the mitochondrial protein Opa1 contributes to mitochondrial damage and cell death caused by oxidative stress. Oxy-proteomics of ischemic-reperfused hearts reveal oxidation of the C-terminal C786 of Opa1 and treatment of perfused mouse hearts, adult cardiomyocytes, and fibroblasts with H₂O₂ leads to the formation of a reduction-sensitive ∼180 KDa Opa1 complex, distinct from the ∼270 KDa one antagonizing cristae remodeling. This Opa1 oxidation process is curtailed by mutation of C786 and of the other 3 Cys residues of its C-terminal domain (Opa1^TetraCys). When reintroduced in Opa1^-/- cell2023-01-01T00:00:00Z2023 Jul2026-05-28T22:50:27.71Z2024-11-20T21:00:52.182ZS-EPMC102202623722469610.1016/j.redox.2023.102755