Figure 10.

Schematic model of mitochondrial-generated ROS stabilization of HIF-1α in hypoxic conditions. Hypoxia increases generation of ROS from the Q_o site of the bc₁ complex. These ROS are released into the intermembrane space and enter the cytosol to decrease PHD activity, thus preventing hydroxylation of the HIF-1α protein. We speculate that ROS decrease the PHD activity from a combination of a posttranslational modification of the PHDs, such as phosphorylation or decreasing the availability of Fe (II), which is required for hydroxylation to occur.