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Intracellular Oxygen Concentration Determined By Mitochondrial Respiration Regulates Production of Reactive Oxygen Species. 线粒体呼吸决定的细胞内氧浓度调节活性氧的产生。
Ara Kim Wiese, Sara Prior, Timothy C Chambers, Masahiro Higuchi

Oxidative phosphorylation not only generates cellular energy via ATP synthesis, but also controls the intracellular oxygen level to minimize oxygen toxicity resulting from reactive oxygen species (ROS). These species include superoxide (O2 -), hydrogen peroxide (H2O2), and hydroxyl radical (•OH). While the rate of mitochondrial respiration determines the intracellular oxygen concentration, the relationship between oxygen concentration and ROS generation is not fully understood. We hypothesized that mitochondrial respiration controls intracellular oxygen concentration which in turn regulates ROS generation. To test this hypothesis, we used two prostate cancer cell lines; PC-3 cells, which have low mitochondrial genome (mtDNA) content and low mitochondrial respiratory activity, and LNCaP cells, which have high mtDNA content and high mitochondrial respiratory activity. PC-3 cells exhibited high mitochondrial oxygen concentration and generated more O2 - as well as •OH when compared to LNCaP cells which showed low mitochondrial oxygen concentration and reduced levels of O2 - and •OH. Exogenous hypoxic conditions (0.2% O2) reduced mitochondrial oxygen concentration and the levels of ROS, whereas exogenous hyperoxic conditions (40% O2) increased mitochondrial oxygen concentration and increased the levels of ROS. These results support the hypothesis that mitochondrial respiration regulates the intracellular oxygen concentration and in turn the generation of ROS.

氧化磷酸化不仅通过ATP合成产生细胞能量,而且还控制细胞内氧水平,以减少活性氧(ROS)引起的氧毒性。这些物质包括超氧化物(O2 -)、过氧化氢(H2O2)和羟基自由基(•OH)。虽然线粒体呼吸速率决定细胞内氧浓度,但氧浓度与ROS生成之间的关系尚不完全清楚。我们假设线粒体呼吸控制细胞内氧浓度,从而调节ROS的产生。为了验证这个假设,我们使用了两种前列腺癌细胞系;PC-3细胞线粒体基因组(mtDNA)含量低,线粒体呼吸活性低,LNCaP细胞mtDNA含量高,线粒体呼吸活性高。与LNCaP细胞相比,PC-3细胞线粒体氧浓度高,产生更多的O2 -和•OH,而LNCaP细胞线粒体氧浓度低,O2 -和•OH水平降低。外源性缺氧条件(0.2% O2)降低了线粒体氧浓度和ROS水平,而外源性高氧条件(40% O2)增加了线粒体氧浓度并增加了ROS水平。这些结果支持了线粒体呼吸调节细胞内氧浓度并进而产生ROS的假设。
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Integrative cancer biology & research
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