title: Manganese ions induce H2O2 generation at the ubiquinone binding site of mitochondrial complex II.
abstract: Manganese-induced toxicity has been recently associated with an increased ROS generation from mitochondrial complex II (succinate:ubiquinone oxidoreductase). To achieve a deeper mechanistic understanding how divalent manganese ions (Mn(2+)) could stimulate mitochondrial ROS production we performed investigations with bovine heart submitochondrial particles (SMP). In succinate fueled SMP, the Mn(2+) induced hydrogen peroxide (H2O2) production was blocked by the specific complex II ubiquinone binding site (IIQ) inhibitor atpenin A5 while a further downstream block at complex III increased the rate markedly. This suggests that site IIQ was the source of the reactive oxygen species. Moreover, Mn(2+) ions also accelerated the rate of superoxide dismutation, explaining the general increase in the measured rates of H2O2 production and an attenuation of direct superoxide detection.
authors.affiliation: Clinic of Anesthesiology, Intensive-Care Medicine and Pain Therapy, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Bonke
authors.affiliation: Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zwicker
authors.affiliation: Clinic of Anesthesiology, Intensive-Care Medicine and Pain Therapy, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany. Electronic address: stefan.droese@kgu.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dröse
mesh_terms: D000818:Animals; D002413:Cations, Divalent; D002417:Cattle; D042963:Electron Transport Complex II / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008345:Manganese / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013367:Submitochondrial Particles / Q000187:drug effects* / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014451:Ubiquinone / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D011728:Pyridones; D017382:Reactive Oxygen Species; C058278:atpenin A5; D014451:Ubiquinone; D008345:Manganese; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III
keywords: Complex II (succinate:ubiquinone oxidoreductase); Manganese; Mitochondria; Reactive oxygen species (ROS); Superoxide dismutation