title: Hypoxia-inducible factors and their roles in energy metabolism.
abstract: Over the course of evolution, aerobic organisms have developed sophisticated systems for responding to alterations in oxygen concentration, as oxygen acts as a final electron acceptor in oxidative phosphorylation for energy production. Hypoxia-inducible factor (HIF) plays a central role in the adaptive regulation of energy metabolism, by triggering a switch from mitochondrial oxidative phosphorylation to anaerobic glycolysis in hypoxic conditions. HIF also reduces oxygen consumption in mitochondria by inhibiting conversion of pyruvate to acetyl CoA, suppressing mitochondrial biogenesis and activating autophagy of mitochondria concomitantly with reduction in reactive oxygen species production. In addition, metabolic reprogramming in response to hypoxia through HIF activation is not limited to the regulation of carbohydrate metabolism; it occurs in lipid metabolism as well. Recent studies using in vivo gene-targeting technique have revealed unexpected, but novel functions of HIF in energy metabolism in a context- and cell type-specific manner, and shed light on the possibility of pharmaceutical targeting HIF as a new therapy against many diseases, including cancer, diabetes, and fatty liver.
authors.affiliation: Department of Life Science and Medical BioScience, School of Advanced Science and Engineering, Waseda University, TWIns Room 02C218, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan. goda@waseda.jp
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
authors.forename: Mai
authors.initials: M
authors.lastname: Kanai
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D004734:Energy Metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism; D010101:Oxygen Consumption; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D051793:Hypoxia-Inducible Factor 1; D019344:Lactic Acid; D019289:Pyruvic Acid