title: The inactivation of mitochondrial F1 ATPase by H2O2 is mediated by iron ions not tightly bound in the protein.
abstract: Exposure to purified mitochondrial F1 ATPase to continuous flux of H2O2 resulted in significant loss (up to 60%) of the ATP hydrolytic activity. The presence of chelating agents including desferrioxamine or previous selective removal of the iron ions not tightly bound in the protein completely prevented the inactivation, whereas re-loading of the enzyme with F3+ restored the sensitivity to H2O2. A marked protective effect was provided as well by mannitol or by Cu,Zn superoxide dismutase. The results indicated the decomposition of H2O2 by redox-active iron-protein adducts as responsible for the enzyme inactivation, probably through site-directed generation of more highly reactive oxygen species. A possible role for iron associated to F1 component in the oxidation, aging and turnover of ATP synthase complex in vivo may be suggested on the basis on these results.
authors.affiliation: Institute of Biology, University of Udine, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Lippe
authors.forename: M
authors.initials: M
authors.lastname: Comelli
authors.forename: D
authors.initials: D
authors.lastname: Mazzilis
authors.forename: F D
authors.initials: FD
authors.lastname: Sala
authors.forename: I
authors.initials: I
authors.lastname: Mavelli
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D008353:Mannitol / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000201:enzymology*; D004369:Pentetic Acid / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D008353:Mannitol; D004369:Pentetic Acid; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D013482:Superoxide Dismutase; D006180:Proton-Translocating ATPases; D003676:Deferoxamine