Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells

Hsin Chen Lee, Pen Hui Yin, Ching You Lu, Chin Wen Chi, Yau Huei Wei*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

473 Scopus citations

Abstract

Mitochondrial respiratory function is impaired in the target tissues of patients with mitochondrial diseases and declines with age in various human tissues. It is generally accepted that respiratory-chain defects result in enhanced production of reactive oxygen species and free radicals in mitochondria. Recently, we have demonstrated that the copy number of mitochondrial DNA (mtDNA) is increased in the lung tissues of elderly human subjects. The mtDNA copy number was suggested to be increased by a feedback mechanism that compensates for defects in mitochondria harbouring mutated mtDNA and a defective respiratory system. However, the detailed mechanism remains unclear. In this study, we treated a human lung fibroblast cell line, MRC-5, with H2O2 at concentrations of 9-360 μM. After the treatment for 24-72 h, we found that cells were arrested at G0 and G1 phases but that mitochondrial mass and mtDNA content were significantly increased in a concentration- and time-dependent manner. Moreover, the oxidative stress induced by buthionine sulphoximine was also found to cause an increase in mitochondrial mass of the treated cells. Increased uptake of a vital mitochondrial dye Rhodamine 123 and enhanced tetrazolium [MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] reduction revealed that the mitochondria increased by H2O2 treatment were functional. In addition, the increase in the mitochondrial mass was also observed in cell-cycle-arrested cells induced by mimosine, lovastatin and genistein. Taken together, these findings suggest that the increase in mitochondrial mass and mtDNA content are the early molecular events of human cells in response to endogenous or exogenous oxidative stress through cell-cycle arrest.

Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalBiochemical Journal
Volume348
Issue number2
DOIs
StatePublished - 01 06 2000
Externally publishedYes

Keywords

  • Aging
  • Cell-cycle arrest
  • Copy number
  • Hydrogen peroxide
  • MtDNA
  • Reactive oxygen species

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