Redox regulation of the hypoxia-inducible factor

Biol Chem. Oct-Nov 2006;387(10-11):1337-46. doi: 10.1515/BC.2006.167.


Reactive oxygen species (ROS) have long been considered only as cyto- and genotoxic. However, there is now compelling evidence that ROS also act as second messengers in response to various stimuli, such as growth factors, hormones and cytokines. The hypoxia-inducible transcription factor (HIF) is a master regulator of oxygen-sensitive gene expression. More recently, HIF has also been shown to respond to non-hypoxic stimuli. Interestingly, recent reports indicate that ROS regulate HIF stability and transcriptional activity in well-oxygenated cells, as well as under hypoxic conditions. Consequently, ROS appear to be key players in regulating HIF-dependent pathways under both normal and pathological circumstances. This review summarizes the current understanding of the role of ROS in the regulation of the mammalian HIF system.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cytosol / metabolism
  • Homeostasis
  • Humans
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Oxygen / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Oxygen