The antioxidant functions of cytochrome c

Low (C(1/2) = 1.5x10^-7 M) concentrations of horse cytochrome c strongly inhibit H₂O₂ production by rat heart mitochondria under conditions of reverse electron transfer from succinate to NAD⁺. The effect is abolished by binding of cytochrome c with liposomes and is not prevented by SOD. Yeast cytochrome c is much less effective than the horse protein whereas acetylated horse cytochrome c is without effect. H₂O₂ formation stimulated by antimycin A is resistant to added cytochrome c. In inside-out submitochondrial vesicles, H₂O₂ production is suppressed by all three cytochrome c samples tested, but at higher concentrations (C(1/2) is about 5x10^-7 M). In vesicles, SOD abolishes the cytochrome c inhibition. We conclude that extramitochondrial cytochrome c is competent in down-regulation of the Complex I H₂O₂ production linked to the reverse electron transfer. Such an effect is absent in the inside-out submitochondrial vesicles where another antioxidant cytochrome c function can be observed, i.e. the oxidation of O₂/(-·) to O₂. A possible role of cytochrome c in the antioxidant defence is discussed.