Role of ubiquinone in the mitochondrial generation of hydrogen peroxide.
Antimycin-inhibited bovine heart submitochondrial particles generate O2- and H2O2 with succinate as electron donor. H2O2 generation involves the action of the mitochondrial superoxide dismutase, in accordance with the McCord & Fridovich [(1969) j. biol. Chem. 244, 6049-6055] reaction mechanism. Removal of ubiquinone by acetone treatment decreases the ability of mitochondrial preparations to generate O2- and H2O2, whereas supplementation of the depleted membranes with ubiquinone enhances the peroxide-generating activity in the reconstituted membranes. Addition of superoxide dismutase to ubiquinone-reconstituted membranes is essential in order to obtain maximal rates of H2O2 generation since the acetone treatment of the membranes apparently inactivates (or removes) the mitochondrial superoxide dismutase. Parallel measurements of H2O2 production, succinate dehydrogenase and succinate-cytochrome c reductase activities show that peroxide generation by ubiquinone-supplemented membranes is a monotonous function of the reducible ubiquinone content, whereas the other two measured activities reach saturation at relatively low concentrations of reducible quinone. Alkaline treatment of submitochondrial particles causes a significant decrease in succinate dehydrogenase activity and succinate-dependent H2O2 production, which contrasts with the increase of peroxide production by the same particles with NADH as electron donor. Solubilized succinate dehydrogenase generates H2O2 at a much lower rate than the parent submitochondrial particles. It is postulated that ubisemiquinone (and ubiquinol) are chiefly responsible for the succinate-dependent peroxide production by the mitochondrial inner membrane.
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002417:Cattle; D006321:Heart / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D010100:Oxygen / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D013384:Succinate Cytochrome c Oxidoreductase / Q000032:analysis; D013385:Succinate Dehydrogenase / Q000032:analysis; D013386:Succinates / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014451:Ubiquinone / Q000378:metabolism* / Q000494:pharmacology
D010743:Phospholipids; D013386:Succinates; D014451:Ubiquinone; D000096:Acetone; D000968:Antimycin A; D006861:Hydrogen Peroxide; D013384:Succinate Cytochrome c Oxidoreductase; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D010100:Oxygen