title: Long chain fatty acyl-CoA modulation of H(2)O (2) release at mitochondrial complex I.
abstract: Complex I is responsible for most of the mitochondrial H(2)O(2) release, low during the oxidation of the NAD linked substrates and high during succinate oxidation, via reverse electron flow. This H(2)O(2) production appear physiological since it occurs at submillimolar concentrations of succinate also in the presence of NAD substrates in heart (present work) and rat brain mitochondria (Zoccarato et al., Biochem J, 406:125-129, 2007). Long chain fatty acyl-CoAs, but not fatty acids, act as strong inhibitors of succinate dependent H(2)O(2) release. The inhibitory effect of acyl-CoAs is independent of their oxidation, being relieved by carnitine and unaffected or potentiated by malonyl-CoA. The inhibition appears to depend on the unbound form since the acyl-CoA effect decreases at BSA concentrations higher than 2 mg/ml; it is not dependent on DeltapH or Deltap and could depend on the inhibition of reverse electron transfer at complex I, since palmitoyl-CoA inhibits the succinate dependent NAD(P) or acetoacetate reduction.
authors.affiliation: Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bortolami
authors.forename: Evelin
authors.initials: E
authors.lastname: Comelato
authors.forename: Franco
authors.initials: F
authors.lastname: Zoccarato
authors.forename: Adolfo
authors.initials: A
authors.lastname: Alexandre
authors.forename: Lucia
authors.initials: L
authors.lastname: Cavallini
mesh_terms: D000818:Animals; D002331:Carnitine / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D042967:Electron Transport Complex I / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D008316:Malonyl Coenzyme A; D009249:NADP; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I; D002331:Carnitine