Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
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DOI：
10.1016/j.cmet.2005.05.001
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发表时间：
2005-06-01
期刊：
影响因子：
29
通讯作者：
Schumacker, PT
中科院分区：
文献类型：
--
作者：
Guzy, RD;Hoyos, B;Schumacker, PT
当氧气（O2）可用性降低时，多细胞生物体启动适应性反应，但O2感测的潜在机制仍然难以捉摸。我们发现，线粒体电子传递链（ETC）的复合物III的功能是HIF-1 α和HIF-2 α的缺氧稳定所必需的。活性氧（ROS）的增加将这种复合物与HIF-α联系起来。稳定化使用RNAi抑制复合物III的Rieske铁硫蛋白的表达，缺氧诱导的HIF-1 α稳定性减弱，并且使用新型ROS敏感的FRET探针测量的ROS产生减少。这些结果表明，线粒体作为O-2传感器的功能和信号缺氧HIF-1 α和HIF-2 α的稳定通过释放ROS到胞质溶胶。
Multicellular organisms initiate adaptive responses when oxygen (02) availability decreases, but the underlying mechanism Of 02 sensing remains elusive. We find that functionality of complex III of the mitochondrial electron transport chain (ETC) is required for the hypoxic stabilization of HIF-1 alpha and HIF-2 alpha. and that an increase in reactive oxygen species (ROS) links this complex to HIF-alpha. stabilization. Using RNAi to suppress expression of the Rieske iron-sulfur protein of complex III, hypoxia-induced HIF-1 alpha stabilization is attenuated, and ROS production, measured using a novel ROS-sensitive FRET probe, is decreased. These results demonstrate that mitochondria function as O-2 sensors and signal hypoxic HIF-1 alpha and HIF-2 alpha stabilization by releasing ROS to the cytosol.