1-Methyl-4-phenylpyridinium (MPP +) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles

We studied the effects of 1-methyl-4-phenylpyridinium (MPP +), a metabolite of a parkinsonism-inducing drug, on the superoxide formation and the lipid peroxidation in bovine heart submitochondrial particles. The NADH-supported formation of superoxide radicals was induced by MPP + at the concentration which is considered to exist in mitochondria of dopamine neurons. The formation increased as the NADH-ubiquinone reductase activity was inhibited by MPP +. The NADH-supported lipid peroxidation by the particles in the presence of ADP-Fe 3+ chelate was also enhanced by MPP + at similar concentrations. The formation was inhibited by succinate and the reduction of endogenous ubiquinone seems to be related to the inhibition. A possibility was discussed that the formation of superoxide anions and the lipid peroxidation may contribute in the cytotoxicity of the drug.