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lüll Hypoxia-inducible factors and the response to hypoxic stress Majmundar AJ; Wong WJ; Simon MCMol Cell 2010[Oct]; 40 (2): 294-309Oxygen (O(2)) is an essential nutrient that serves as a key substrate in cellular metabolism and bioenergetics. In a variety of physiological and pathological states, organisms encounter insufficient O(2) availability, or hypoxia. In order to cope with this stress, evolutionarily conserved responses are engaged. In mammals, the primary transcriptional response to hypoxic stress is mediated by the hypoxia-inducible factors (HIFs). While canonically regulated by prolyl hydroxylase domain-containing enzymes (PHDs), the HIFalpha subunits are intricately responsive to numerous other factors, including factor-inhibiting HIF1alpha (FIH1), sirtuins, and metabolites. These transcription factors function in normal tissue homeostasis and impinge on critical aspects of disease progression and recovery. Insights from basic HIF biology are being translated into pharmaceuticals targeting the HIF pathway.|*Signal Transduction[MESH]|Animals[MESH]|Basic Helix-Loop-Helix Transcription Factors/*metabolism[MESH]|Cell Hypoxia/physiology[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism[MESH]|Hypoxia/physiopathology[MESH]|Models, Biological[MESH]|Neoplastic Stem Cells/metabolism[MESH]|Stress, Physiological/*physiology[MESH] |