Fig. 2

Mitochondrial cholesterol-mediated HIF1α stabilization. Mitochondrial cholesterol loading mediated by StARD1 decreases mitochondrial membrane fluidity which leads to an impaired activity of the OGC, which exchanges mitochondrial 2-OG by cytosolic GSH. Cytosolic 2-OG depletion may promote HIF1α stabilization by the impairment of PHD due to their requirement of 2-OG as a cofactor for HIF1α hydroxylation and subsequent degradation. Moreover, 2-OGC inhibition results in mGSH depletion, which in turn, limits the detoxification of ROS, in particular, H₂O₂. The subsequent increase in ROS and oxidative stress impact negatively on PHD, resulting in HIF1α stabilization