Turning the Oxygen Dial: Balancing the Highs and Lows

Trends Cell Biol. 2020 Jul;30(7):516-536. doi: 10.1016/j.tcb.2020.04.005. Epub 2020 May 5.


Oxygen is both vital and toxic to life. Molecular oxygen is the most used substrate in the human body and is required for several hundred diverse biochemical reactions. The discovery of the PHD-HIF-pVHL system revolutionized our fundamental understanding of oxygen sensing and cellular adaptations to hypoxia. It deepened our knowledge of the biochemical underpinnings of numerous diseases, ranging from anemia to cancer. Cellular dysfunction and tissue pathology can result from a mismatch of oxygen supply and demand. Recent work has shown that mitochondrial disease models display tissue hyperoxia and that disease pathology can be reversed by normalization of excess oxygen, suggesting that certain disease states can potentially be treated by modulating oxygen levels. In this review, we describe cellular and organismal mechanisms of oxygen sensing and adaptation. We provide a revitalized framework for understanding pathologies of too little or too much oxygen.

Keywords: hyperoxia; hypoxia; oxygen adaptation; oxygen metabolism; oxygen sensing.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Hypoxia / drug effects
  • Cells / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Models, Biological
  • Oxygen / metabolism*
  • Oxygen / toxicity


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oxygen