From Polyps to People: A Highly Familiar Response to Hypoxia

Ann N Y Acad Sci. 2009 Oct;1177:19-29. doi: 10.1111/j.1749-6632.2009.05035.x.

Abstract

Obligate aerobes, by definition, require oxygen in order to sustain life. Therefore, changes in environment or physiology that cause metabolic demand for oxygen to exceed supply (hypoxia) can be highly detrimental. Despite considerable variation in physiology and habitat between species, a majority of metazoa employ homologues of the hypoxia-inducible factor (HIF) transcription factors to adapt to oxygen deprivation. Studies in mammals, Drosophila and C. elegans have shown that regulation of HIF-alpha by prolyl hydroxylase (PHD)-mediated proteasomal degradation is conserved, as are a number of HIF target genes. More recently, analysis of coral and beetle HIFs has revealed that, unlike flies and worms, the C-terminal transactivation domain of HIF-alpha and its regulatory hydroxylase FIH-1 are also preserved. The reasons for variable conservation of this system are unknown. However, discovery of the "intermediary" properties of the beetle HIF pathway may prove a useful tool to better define HIF signaling in both mammals and invertebrates.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Drosophila melanogaster
  • Humans
  • Hypoxia / physiopathology*
  • Hypoxia-Inducible Factor 1 / metabolism
  • Hypoxia-Inducible Factor 1 / physiology
  • Mixed Function Oxygenases / metabolism
  • Mixed Function Oxygenases / physiology
  • Procollagen-Proline Dioxygenase / metabolism
  • Procollagen-Proline Dioxygenase / physiology
  • Tribolium

Substances

  • Hypoxia-Inducible Factor 1
  • Mixed Function Oxygenases
  • Procollagen-Proline Dioxygenase