Searching for molecular hypoxia sensors among oxygen-dependent enzymes

Elife. 2023 Jul 26:12:e87705. doi: 10.7554/eLife.87705.

Abstract

The ability to sense and respond to changes in cellular oxygen levels is critical for aerobic organisms and requires a molecular oxygen sensor. The prototypical sensor is the oxygen-dependent enzyme PHD: hypoxia inhibits its ability to hydroxylate the transcription factor HIF, causing HIF to accumulate and trigger the classic HIF-dependent hypoxia response. A small handful of other oxygen sensors are known, all of which are oxygen-dependent enzymes. However, hundreds of oxygen-dependent enzymes exist among aerobic organisms, raising the possibility that additional sensors remain to be discovered. This review summarizes known and potential hypoxia sensors among human O2-dependent enzymes and highlights their possible roles in hypoxia-related adaptation and diseases.

Keywords: cell biology; hypoxia; hypoxia sensors; oxygen; oxygen-dependent enzymes.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia
  • Gene Expression Regulation
  • Humans
  • Hypoxia*
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oxygen* / metabolism
  • Procollagen-Proline Dioxygenase / genetics
  • Transcription Factors / metabolism

Substances

  • Oxygen
  • Transcription Factors
  • Procollagen-Proline Dioxygenase
  • Hypoxia-Inducible Factor 1, alpha Subunit