title: Ferricytochrome c protects mitochondrial cytochrome c oxidase against hydrogen peroxide-induced oxidative damage.
abstract: An excess of ferricytochrome c protects purified mitochondrial cytochrome c oxidase and bound cardiolipin from hydrogen peroxide-induced oxidative modification. All of the peroxide-induced changes within cytochrome c oxidase, such as oxidation of Trp(19,IV) and Trp(48,VIIc), partial dissociation of subunits VIa and VIIa, and generation of cardiolipin hydroperoxide, no longer take place in the presence of ferricytochrome c. Furthermore, ferricytochrome c suppresses the yield of H(2)O(2)-induced free radical detectable by electron paramagnetic resonance spectroscopy within cytochrome c oxidase. These protective effects are based on two mechanisms. The first involves the peroxidase/catalase-like activity of ferricytochrome c, which results in the decomposition of H(2)O(2), with the apparent bimolecular rate constant of 5.1±1.0M(-1)s(-1). Although this value is lower than the rate constant of a specialized peroxidase, the activity is sufficient to eliminate H(2)O(2)-induced damage to cytochrome c oxidase in the presence of an excess of ferricytochrome c. The second mechanism involves ferricytochrome c-induced quenching of free radicals generated within cytochrome c oxidase. These results suggest that ferricytochrome c may have an important role in protection of cytochrome c oxidase and consequently the mitochondrion against oxidative damage.
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Sedlák
authors.forename: Marian
authors.initials: M
authors.lastname: Fabian
authors.forename: Neal C
authors.initials: NC
authors.lastname: Robinson
authors.forename: Andrej
authors.initials: A
authors.lastname: Musatov
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000378:metabolism; D002417:Cattle; D045304:Cytochromes c / Q000737:chemistry* / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D010084:Oxidation-Reduction
chemical_list: D002308:Cardiolipins; D005609:Free Radicals; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV
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