Figure 8.

HIFs regulate adaptation to hypoxia. Multiple inputs, including hypoxia, ROS, TCA metabolites (succinate and fumarate), and NO, inhibit prolyl hydroxlases (PHDs) to activate hypoxia inducible factors (HIFs). At the organismal level, HIFs stimulate angiogenesis, erythropoiesis, and ventilation to increase oxygen delivery. At the cellular level, HIFs diminish oxidative phosphorylation and increase glycolysis. HIFs also suppress ATP-consuming generation to preserve a high ATP/ADP ratio in cells. (Adapted from Kaelin and Ratcliffe 2008.)