Guzy Robert D, Hoyos Beatrice, Robin Emmanuel, Chen Hong, Liu Liping, Mansfield Kyle D, Simon M Celeste, Hammerling Ulrich, Schumacker Paul T
Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
Cell Metab. 2005 Jun;1(6):401-8. doi: 10.1016/j.cmet.2005.05.001.
Multicellular organisms initiate adaptive responses when oxygen (O(2)) availability decreases, but the underlying mechanism of O(2) 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.
当氧气（O₂）供应减少时，多细胞生物会启动适应性反应，但氧气感知的潜在机制仍不清楚。我们发现，线粒体电子传递链（ETC）复合物III的功能对于缺氧时HIF-1α和HIF-2α的稳定是必需的，并且活性氧（ROS）的增加将该复合物与HIF-α的稳定联系起来。使用RNA干扰抑制复合物III的Rieske铁硫蛋白的表达，缺氧诱导的HIF-1α稳定减弱，并且使用新型ROS敏感FRET探针测量的ROS产生减少。这些结果表明，线粒体作为氧气传感器，通过向细胞质释放ROS来信号传导缺氧时HIF-1α和HIF-2α的稳定。
