Figure 6.

Schematic view of HIF-1α and the intrinsic triggering pathway of the apoptotic signaling cascade. Hypoxia stimulates the HIF-1α and mitochondrial apoptotic signaling pathway and triggers the release of cyto-c from the mitochondrial matrix to the cytoplasm, thereby binding to the Apaf-1 protein, inducing its conformational change and activating it. Thus, the apoptosome consisting of cyto-c/Apaf-1/caspase-9 is yielded and is able to cleave or activate the executioner caspase-3. The activated caspase-3 complex then results in apoptosis. C9, caspase-9; C3, caspase-3; HIF-1α, hypoxia inducible factor-1α; cyto-c, cytochrome c; Apaf-1, apoptotic protease activating factor-1; CARD, caspase recruitment domain containing; Bak, Bcl2 antagonist/killer; Bax, Bcl-2-associated X protein; Bcl-2, Bcl2, apoptosis regulator; CBP, CREB binding protein; HIF-1β, hypoxia inducible factor-1β; HNF4, hepatocyte nuclear factor 4α.