How do cells adapt to oxygen availability – the role of hypoxia-inducible factor HIF-1

Abstract

Thanks to the works of this year`s Nobel Laureates, we know much more about how different oxygen levels regulate fundamental physiological and pathophysiological processes. Variable oxygen availability requires the activation of multiple adaptation processes from cells. Inhibition of the degradation of α subunit of the hypoxia-inducible factor (HIF-1) is a key reaction of cells to hypoxic conditions. These conditions lead to generation of the active transcription factor – dimer HIF-1α/β, which activates the expression of plenty of genes. HIF-1 is then accumulated in the nucleus and binded to DNA in hypoxia-regulated genes. The products of these genes are involved in generation of new blood vessels (VEGF), erytropoesis process (EPO) and in energy metabolism in mitochondria from oxidative phosphorylation to aerobic glycolysis (LDH, phosphoglycero kinase, aldolase and GLUT1).