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 90-360 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.
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June 2000
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Research Article|
May 23 2000
Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells
Hsin-Chen LEE;
Hsin-Chen LEE
*Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Pen-Hui YIN;
Pen-Hui YIN
†Institute of Pharmacology, National Yang-Ming University and Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan 112, Republic of China
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Ching-You LU;
Ching-You LU
*Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Chin-Wen CHI;
Chin-Wen CHI
†Institute of Pharmacology, National Yang-Ming University and Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan 112, Republic of China
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Yau-Huei WEI
Yau-Huei WEI
1
*Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
1To whom correspondence should be addressed (e-mail joeman@;mailsrv.ym.edu.tw).
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Publisher: Portland Press Ltd
Received:
September 30 1999
Revision Received:
March 08 2000
Accepted:
March 29 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 348 (2): 425–432.
Article history
Received:
September 30 1999
Revision Received:
March 08 2000
Accepted:
March 29 2000
Citation
Hsin-Chen LEE, Pen-Hui YIN, Ching-You LU, Chin-Wen CHI, Yau-Huei WEI; Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J 1 June 2000; 348 (2): 425–432. doi: https://doi.org/10.1042/bj3480425
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