- 作者: Hsin-Chen Lee a,c, Pen-Hui Yin b,d, Chin-Wen Chi b,d, Yau-Huei Wei a
- 作者服務機構: a Department of Biochemistry and Center for Cellular and Molecular Biology, b Institute of Pharmacology, National Yang-Ming University, Taipei, c Institute of Biochemistry, Chung-Shan Medical University, Taichung, d Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: Abnormal proliferation of mitochondria generally occursin muscle of aged individuals and patients with mito-chondrial myopathy. An increase in the mitochondrialDNA (mtDNA) copy number has also been observed inaging human tissues. However, the molecular mecha-nism underlying the increase in mitochondrial mass andmtDNA is still unclear. In a previous study, we demon-strated that sublethal levels of oxidative stress caused anincrease in mitochondrial mass in human lung cells. Inthis communication, we report our recent findings thatthe mitochondrial mass in human lung fibroblasts (MRC-5) in a later proliferation stage is significantly increasedcompared to that in the early stages of proliferation. Theextent of the increase in mitochondrial mass in thesenescent cells was similar to that in cells in the earlystages of proliferation that had been treated with lowconcentrations ( 180 H of hydrogen peroxide (H 0 ).Moreover, we found that the rate of reactive oxygen spe-cies (ROS) production was higher in cells in the later pro-liferation stage compared to cells in the early prolifera-tion stages. A similar phenomenon was also observed incells in the early proliferation stages under low levels ofoxidative stress. On the other hand, the mRNA levels ofmany nuclear DNA-encoded proteins involved in mito-chondrial biogenesis, particularly nuclear respiratoryfactor-1, were found to increase in cells in later prolifera-tion stages and in cells in early proliferation stages thathad been treated with 180 M H 0 . Interestingly, theincrease in mitochondrial mass in the cells under oxida-tive stress could be repressed by treatment with cyclo-heximide or m-chlorocarbonyl cyanide phenylhydrazonebut not by chloramphenicol. Furthermore, the mitochon-drial mass of mtDNA-less p cells was also significant-1y increased by exposure to low concentrations (e.g.180 M of H O . These results suggest that the increasein mitochondrial mass in replicative senescent cells mayresult from an increase in ROS production, and that it isdependent on both de novo synthesis of nuclear DNA-encoded proteins and their import into mitochondria,dictated by the membrane potential of mitochondria.
- 中文關鍵字: --
- 英文關鍵字: Oxidative stress, Aging, Senescence, Mitochondria, Nuclear respiratory factor, Mitochondrial DNA