Oxygen Tolerance and Coupling of Mitochondrial Electron Transport

• Published in: The Journal of biological chemistry Vol. 279; no. 45; pp. 46580 - 46587
• Main Authors: Campian, Jian Li, Qian, Mingwei, Gao, Xueshan, Eaton, John W
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 05.11.2004
• Subjects: Aconitate Hydratase - metabolism; Antioxidants - pharmacology; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology; Cell Proliferation; Citrate (si)-Synthase - metabolism; Edetic Acid - pharmacology; Electron Transport; Electron Transport Complex IV - metabolism; Electrons; Glucose - metabolism; Glutamine - metabolism; HeLa Cells; Humans; Ionophores - pharmacology; Lactates - metabolism; Mitochondria - metabolism; Oxygen - metabolism; Oxygen Consumption; Partial Pressure; Peroxides - metabolism; Protoporphyrins - metabolism; Reactive Oxygen Species; Spectrometry, Fluorescence; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M406685200

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 “HeLa-80,” was derived from wild-type HeLa cells (“HeLa-20”) 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 (∼2-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 (∼2-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.