Figure 7
From: HIF-independent role of prolyl hydroxylases in the cellular response to amino acids
Model for oxygen- and nutrient-sensing mechanisms by PHDs. Left side: PHDs mediate the inhibition of HIF in the presence of oxygen. Under hypoxia, lack of oxygen inhibits PHD activity, resulting in the stabilization of HIF, which inhibits mTORC1 via REDD1 induction. Right side: PHDs are required for the activation of mTORC1 in the presence of amino acids. Under amino-acid starvation, lack of αKG inhibits PHD activity, resulting in the inhibition of mTORC1, hence a reduction in HIF expression. Loss of PHD activity can also mediate the induction of autophagy under amino-acid starvation conditions in a HIF-independent manner.
