eLife (Jul 2023)

Searching for molecular hypoxia sensors among oxygen-dependent enzymes

  • Li Li,
  • Susan Shen,
  • Philip Bickler,
  • Matthew P Jacobson,
  • Lani F Wu,
  • Steven J Altschuler

DOI
https://doi.org/10.7554/eLife.87705
Journal volume & issue
Vol. 12

Abstract

Read online

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