The content of intracellular mitochondrial DNA is decreased by 1- methyl-4-phenylpyridinium ion (MPP+)

Kenichi Miyako, Yoichiro Kai, Takashi Irie, Koichiro Takeshige, Dongchon Kang

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

1-Methyl-4-phenylpyridinium ion (MPP+), an oxidative metabolite of 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is considered to be directly responsible for MPTP-induced Parkinson's disease-like symptoms by inhibiting NADH-ubiquinone oxidoreductase (complex I) in the mitochondrial respiratory chain. Here we demonstrate that 25 μm MPP+ decreases the content of mitochondrial DNA to about one-third in HeLa S3 cells. On the contrary, 0.1 μM rotenone, which inhibits complex I to the same extent as 25 μM MPP+ in the cells, increases the content of mitochondrial DNA about 2- fold. Hence, the effect of MPP+ on mitochondrial DNA is not mediated by the inhibition of complex I. To examine the replication state of mitochondrial DNA, we measured the amount of nascent strands of mitochondrial DNA. The amount is decreased by MPP+ but increased by rotenone, suggesting that the replication of mitochondrial DNA is inhibited by MPP+. Because the proper amount of mitochondrial DNA is essential to maintain components of the respiratory chain, the decrease of mitochondrial DNA may play a role in the progression of MPTP-induced Parkinson's disease-like symptoms caused by the mitochondrial respiratory failure.

Original languageEnglish
Pages (from-to)9605-9608
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number15
DOIs
Publication statusPublished - Apr 11 1997

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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