Intracellular Oxygen Concentration Determined By Mitochondrial Respiration Regulates Production of Reactive Oxygen Species.
Intracellular Oxygen Concentration Determined By Mitochondrial Respiration Regulates Production of Reactive Oxygen Species.
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发表时间：
2017
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通讯作者：
Ara Kim Wiese;Sara E. Prior;T. Chambers;M. Higuchi
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作者：
Ara Kim Wiese;Sara E. Prior;T. Chambers;M. Higuchi
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最小化由活性氧（ROS）引起的氧毒性。这些物种包括超氧化物（O2 -），过氧化氢（H2 O2）和羟基自由基（·OH）。虽然线粒体呼吸的速率决定了细胞内的氧浓度，但氧浓度和ROS产生之间的关系尚未完全了解。我们假设线粒体呼吸控制细胞内氧浓度，进而调节ROS的产生。为了验证这一假设，我们使用了两种前列腺癌细胞系; PC-3细胞，其具有低线粒体基因组（mtDNA）含量和低线粒体呼吸活性，以及LNCaP细胞，其具有高mtDNA含量和高线粒体呼吸活性。PC-3细胞表现出较高的线粒体氧浓度，并产生更多的O2 -和·OH相比，LNCaP细胞表现出较低的线粒体氧浓度和水平的O2 -和·OH的减少。外源性低氧条件（0.2%O2）降低线粒体氧浓度和ROS水平，而外源性高氧条件（40%O2）增加线粒体氧浓度和增加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调节ROS产生的假设。
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.