Oxygen Tolerance and Coupling of Mitochondrial Electron Transport
Oxygen is critical to aerobic metabolism, but excessive oxygen (hyperoxia) causes cell injury and death. An oxygen-tolerant strain of HeLa cells, which proliferates even under 80% O 2 , termed âHeLa-80,â was derived from wild-type HeLa cells (âHeLa-20â) by selection for resistance to stepwis...
Saved in:
Published in | The Journal of biological chemistry Vol. 279; no. 45; pp. 46580 - 46587 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
05.11.2004
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Oxygen is critical to aerobic metabolism, but excessive oxygen (hyperoxia) causes cell injury and death. An oxygen-tolerant
strain of HeLa cells, which proliferates even under 80% O 2 , termed âHeLa-80,â was derived from wild-type HeLa cells (âHeLa-20â) by selection for resistance to stepwise increases of
oxygen partial pressure. Surprisingly, antioxidant defenses and susceptibility to oxidant-mediated killing do not differ between
these two strains of HeLa cells. However, under both 20 and 80% O 2 , intracellular reactive oxygen species (ROS) production is significantly (â¼2-fold) less in HeLa-80 cells. In both cell lines
the source of ROS is evidently mitochondrial. Although HeLa-80 cells consume oxygen at the same rate as HeLa-20 cells, they
consume less glucose and produce less lactic acid. Most importantly, the oxygen-tolerant HeLa-80 cells have significantly
higher cytochrome c oxidase activity (â¼2-fold), which may act to deplete upstream electron-rich intermediates responsible for ROS generation.
Indeed, preferential inhibition of cytochrome c oxidase by treatment with n -methyl protoporphyrin (which selectively diminishes synthesis of heme a in cytochrome c oxidase) enhances ROS production and abrogates the oxygen tolerance of the HeLa-80 cells. Thus, it appears that the remarkable
oxygen tolerance of these cells derives from tighter coupling of the electron transport chain. |
---|---|
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M406685200 |