(A), In the presence of normoxia and iron abundance, HIF1α undergoes hydroxylation by active form of prolyl hydroxylase, which requires oxygen and iron cofactors. This is followed by proteasomal degradation of HIF1α mediated by ubiquitin ligase. (B), Limitation of oxygen and iron, characteristic of injured and ischemic tissues, are essential for post-translational HIF1α stabilization and accumulation, affecting gene transcription.