REVIEW MAMMALIAN OXYGEN SENSING, SIGNALLING AND GENE REGULATION

Oxygen is essential to the life of all aerobic organisms. Virtually every cell type is able to sense a limited oxygen supply (hypoxia) and specifically to induce a set of oxygenregulated genes. This review summarizes current concepts of mammalian oxygen-sensing and signal-transduction pathways. Since the discovery of the hypoxia-inducible factors (HIFs), a great deal of progress has been made in our comprehension of how hypoxia induces the expression of oxygen-regulated genes. The α subunit of the heterodimeric transcription factors HIF-1, 2 and 3 is unstable under normoxia but is rapidly stabilized upon exposure to hypoxic conditions. Following heterodimerization with the constitutively expressed β subunit, HIFs activate the transcription of an increasing number of genes involved in maintaining oxygen homeostasis at the cellular, local and systemic levels.