Inhibition of ATP synthesis by 1-methyl-4-phenylpyridinium ion (MPP+) in isolated mitochondria from mouse brains.

Effect of 1-methyl-4-phenylpyridinium ion (MPP+) on adenosine triphosphate (ATP) synthesis was studied using isolated mitochondrial preparations from mouse brains. Oxidation of glutamate + malate in the mitochondria estimated by polarography was significantly inhibited by MPP+, and synthesis of ATP was inhibited to approximately 9% of that of control by 0.06 mM of MPP+. Oxidation of alpha-glycerophosphate and succinate was not inhibited, and ATP was synthesized normally. Energy crisis appears to be one of the most important mechanisms of neuronal degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced experimental parkinsonism.