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Cadenas E, Boveris A: Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria. Biochem J. 1980 Apr 15;188(1):31-7.
Rat and pigeon heart mitochondria supplemented with antimycin produce 0.3-1.0nmol of H (2) O (2)/min per mg of protein. These rates are stimulated up to 13-fold by addition of protophores (carbonyl cyanide p-trifluoromethoxyphenylhydrazone, carbonyl cyanide m-chloromethoxyphenylhydrazone and pentachlorophenol). Ionophores, such as valinomycin and gramicidin, and Ca (2+) also markedly stimulated H (2) O (2) production by rat heart mitochondria. The enhancement of H (2) O (2) generation in antimycin-supplemented mitochondria and the increased O (2) uptake of the State 4-to-State 3 transition showed similar protophore, ionophore and Ca (2+) concentration dependencies. Thenoyltrifluoroacetone and N-bromosuccinimide, which inhibit succinate-ubiquinone reductase activity, also decreased mitochondrial H (2) O (2) production. Addition of cyanide to antimycin-supplemented beef heart submitochondrial particles inhibited the generation of O (2) (-), the precursor of mitochondrial H (2) O (2). This effect was parallel to the increase in cytochrome c reduction and it is interpreted as indicating the necessity of cytochrome c (1) (3+) to oxidize ubiquinol to ubisemiquinone, whose autoxidation yields O (2) (-). The effect of protophores, ionophores and Ca (2+) is analysed in relation to the propositions of a cyclic mechanism for the interaction of ubiquinone with succinate dehydrogenase and cytochromes b and c (1) [Wikstrom & Berden (1972) Biochim. Biophys. Acta283, 403-420; Mitchell (1976) J. Theor. Biol.62, 337-367]. A collapse in membrane potential, increasing the rate of ubisemiquinone formation and O (2) (-) production, is proposed as the molecular mechanism for the enhancement of H (2) O (2) formation rates observed on addition of protophores, ionophores and Ca (2+). |
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