Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: Protective effect of coenzyme Q10

Younghye Moon, Kun Ho Lee, June Hee Park, Dongho Geum, Kyungjin Kim

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Chronic exposure to the pesticide rotenone induces a selective degeneration of nigrostriatal dopaminergic neurons and reproduces the features of Parkinson's disease in experimental animals. This action is thought to be relevant to its inhibition of the mitochondrial complex I, but the precise mechanism of this suppression in selective neuronal death is still elusive. Here we investigate the mechanism of dopaminergic neuronal death mediated by rotenone in primary rat mesencephalic neurons. Low concentrations of rotenone (5-10 nM) induce the selective death of dopaminergic neurons without significant toxic effects on other mesencephalic cells. This cell death was coincident with apoptotic events including capsase-3 activation, DNA fragmentation, and mitochondrial membrane depolarization. Pretreatment with coenzyme Q 10, the electron transporter in the mitochondrial respiratory chain, remarkably reduced apoptosis as well as the mitochondrial depolarization induced by rotenone, but other free radical scavengers such as N-acetylcysteine, glutathione, and vitamin C did not. Furthermore, the selective neurotoxicity of rotenone was mimicked by the mitochondrial protonophore carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), a cyanide analog that effectively collapses a mitochondrial membrane potential. These data suggest that mitochondrial depolarization may play a crucial role in rotenone-induced selective apoptosis in rat primary dopaminergic neurons.

Original languageEnglish
Pages (from-to)1199-1208
Number of pages10
JournalJournal of Neurochemistry
Volume93
Issue number5
DOIs
Publication statusPublished - 2005 Jun

Keywords

  • Coenzyme Q
  • Dopaminergic neurons
  • Mitochondrial membrane potential
  • Parkinson's disease
  • Rotenone

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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