Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity by 1-methyl-4-phenylpyridinium ion.

Effect of 1-methyl-4-phenylpyridinium ion (MPP+) on the activity of NADH-ubiquinone oxidoreductase was studied using mitochondria prepared from rat brains. At first, inhibition of oxygen consumption by MPP+ with pyruvate + malate or glutamate + malate as substrates was confirmed polarographically using a Clark-type oxygen electrode. Then, activity of NADH-ubiquinone oxidoreductase in the same samples used in polarography was assayed. Incubation of mitochondria with 0.05 mM of MPP+ together with glutamate, malate and ADP resulted in approximately 50% inhibition of NADH-ubiquinone oxidoreductase activity. Significance of the results was discussed with respect to the mechanism of neuronal degeneration by MPP+.