Hypoxia-inducible factors and their roles in energy metabolism

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)457-463
Number of pages7
JournalInternational Journal of Hematology
Volume95
Issue number5
DOIs
Publication statusPublished - 2012 May

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Energy Metabolism
Oxidative Phosphorylation
Mitochondria
Oxygen
Acetyl Coenzyme A
Gene Targeting
Autophagy
Carbohydrate Metabolism
Organelle Biogenesis
Glycolysis
Fatty Liver
Liver Neoplasms
Pyruvic Acid
Lipid Metabolism
Oxygen Consumption
Hypoxia
Reactive Oxygen Species
Electrons
Pharmaceutical Preparations

Keywords

  • Glycolysis
  • HIF
  • Lipid metabolism
  • Mitochondria

ASJC Scopus subject areas

  • Hematology

Cite this

Hypoxia-inducible factors and their roles in energy metabolism. / Goda, Nobuhito; Kanai, Mai.

In: International Journal of Hematology, Vol. 95, No. 5, 05.2012, p. 457-463.

Research output: Contribution to journalArticle

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