Hypoxia-inducible factors and the response to hypoxic stress

Mol Cell. 2010 Oct 22;40(2):294-309. doi: 10.1016/j.molcel.2010.09.022.

Abstract

Oxygen (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 HIFα subunits are intricately responsive to numerous other factors, including factor-inhibiting HIF1α (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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Hypoxia / physiology
  • Humans
  • Hypoxia / physiopathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Models, Biological
  • Neoplastic Stem Cells / metabolism
  • Signal Transduction*
  • Stress, Physiological / physiology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • endothelial PAS domain-containing protein 1