title: [Superoxide formation and lipid peroxidation by the mitochondrial electron-transfer chain].
abstract: Isolated mitochondria supplemented with succinate or NAD(+)-linked substrates generate hydrogen peroxide (H2O2) in State 4 and the generation is enhanced by antimycin A, an inhibitor of the respiratory chain. Superoxide is a stoichiometric precursor of mitochondrial H2O2 because the ratio of O2-/H2O2 generation rates is close to 2.0 and is generated by an autoxidizable component in the NADH dehydrogenase and the ubiquinone-cytochrome b site. Lipid peroxidation is a free radical-mediated degradation of polyunsaturated fatty acids. Lipid-peroxidation reactions by bovine submitochondrial particles are supported by NADH or NADPH in the presence of ADP-Fe3+ chelate. Electrons from NADH are supplied to the reactions from a component between the substrate site and the rotenone-sensitive site of the NADH dehydrogenase. The peroxidation is dependent on the rate of electron input into the respiratory chain and on the concentration of reduced ubiquinone. Alteration of inner-membrane components and damage to electron-transfer activities of submitochondrial particles are induced by lipid peroxidation. 1-Melhyl-4-phenylpyridinium (MPP+), a metabolite of a parkinsonism-inducing drug, induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in submitochondrial particles, indicating that the oxidative stress induced by MPP+ may potentiate its toxicity in dopamine neurons.
authors.affiliation: Department of Biochemistry, Kyushu University School of Medicine.
authors.forename: K
authors.initials: K
authors.lastname: Takeshige
mesh_terms: D004579:Electron Transport; D006801:Humans; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D010300:Parkinson Disease / Q000209:etiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides