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

Biochem Biophys Res Commun. 1990 Aug 16;170(3):1049-55. doi: 10.1016/0006-291x(90)90498-c.


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-Fe3+ 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology*
  • Animals
  • Cattle
  • Free Radicals
  • Lipid Peroxidation / drug effects*
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • NAD / pharmacology
  • Submitochondrial Particles / drug effects*
  • Submitochondrial Particles / metabolism
  • Superoxides / metabolism*


  • Free Radicals
  • NAD
  • Superoxides
  • 1-Methyl-4-phenylpyridinium