Proton leak induced by reactive oxygen species pro

Authors: Rachel Navet Ange MouithysMickalad Pierre Douette Claudine M SluseGoffart Wieslawa Jarmuszkiewicz Francis E Sluse

Publish Date: 2006/05/30

Volume: 38, Issue: 1, Pages: 23-32

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Abstract

Superoxide anion generation and the impairment of oxidative phosphorylation yield were studied in rat skeletal muscle mitochondria submitted to anoxia/reoxygenationk in vitro Production of superoxide anion was detected after several cycles of anoxia/reoxygenationk Concomitantly a decrease of state 3 respiration and phosphorylation yield ADP/O were observed The latter resulted from a proton leak The presence of palmitic acid during anoxia/reoxygenationk cycles led to a dosedependent inhibition of superoxide anion production together with a partial protection of the ADP/O ratio measured after anoxia/reoxygenationk The ADP/O decrease was shown to be due to a permeability transition poresustained proton leak as it was suppressed by cyclosporine A The permeability transition pore activation was induced during anoxia/reoxygenationk by superoxide anion as it was cancelled by the spin trap POBN which scavenges superoxide anion and by palmitic acid which induces mitochondrial uncoupling It can be proposed that the palmitic acidinduced proton leak cancels the production of superoxide anion by mitochondria during anoxia/reoxygenationk and therefore prevents the occurrence of the superoxide anioninduced permeability transition poremediated proton leak after anoxia/reoxygenationk

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