Fig. 4
a Evolution of genes encoding the hypoxia-inducible factor (HIF) pathway and (b). Importance of mitochondrial-generated reactive oxygen species (ROS) stabilization of HIF-1α during hypoxia including emergent quantum signaling aspects. a Appearance of genes based on published approximations (Taylor and McElwain 2010). b During normoxia, hypoxia-inducible factor-1 alpha (HIF-1α) is hydroxylated on prolines by the prolyl hydroxylases (PHD), tagging it for recognition by the von Hippel Lindau tumor suppressor protein (VHL) resulting in the continual ubiquitination and degradation of HIF-1α. During hypoxia, the mitochondrial formation of the superoxide anion from the Qo site of the bc1 complex of Complex III are released into the intermembrane space and enter the cytosol to decrease PHD activity preventing hydroxylation resulting in HIF-1α stabilization and transcription of genes that collectively preserve cerebral oxygen (O2) homeostasis. Note that emerging “quantum” aspects of cerebral O2 sensing are also outlined. FIH, factor inhibiting HIF; CBP, cyclic AMP-response element binding protein; HRE, hypoxia response element