title: Evidence that the blockade of mitochondrial respiration by the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) involves binding at the same site as the respiratory inhibitor, rotenone.
abstract: It has been postulated that 1-methyl-4-phenylpyridinium (MPP+) blocks mitochondrial respiration by combining at the same site as rotenone, a potent inhibitor of NADH oxidation in mitochondria, known to act at the junction of NADH dehydrogenase and coenzyme Q (CoQ). The present experiments show that MPP+ and two of its analogs indeed act in a concentration dependent manner to prevent the binding of [14C]-rotenone to submitochondrial particles (ETP) and significantly decrease the inhibition of electron transport caused by rotenone. It therefore appears that MPP+ binds at the same site as rotenone or an adjacent site, supporting the hypothesis that its neurotoxic action is due to the inhibition of mitochondrial respiration.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
authors.forename: M J
authors.initials: MJ
authors.lastname: Krueger
authors.forename: T P
authors.initials: TP
authors.lastname: Singer
authors.forename: J E
authors.initials: JE
authors.lastname: Casida
authors.forename: R R
authors.initials: RR
authors.lastname: Ramsay
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D004579:Electron Transport; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D012402:Rotenone / Q000378:metabolism* / Q000494:pharmacology; D013367:Submitochondrial Particles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D012402:Rotenone; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D015655:1-Methyl-4-phenylpyridinium