Hypoxia-induced autophagy: cell death or cell survival?

Curr Opin Cell Biol. 2010 Apr;22(2):177-80. doi: 10.1016/j.ceb.2009.11.015. Epub 2009 Dec 21.


Hypoxia (approximately 3-0.1% oxygen) is capable of rapidly inducing, via the hypoxia-inducible factor (HIF-1), a cell survival response engaging autophagy. This process is mediated by the atypical BH3-only proteins the Bcl-2/E1B 19kDa-interacting protein 3 (BNIP3/BNIP3L (NIX)) that are induced by HIF-1. These mitochondrial associated BNIP proteins also mediate mitophagy, a metabolic adaptation for survival that is able to control reactive oxygen species (ROS) production and DNA damage. In contrast, severe hypoxic conditions or anoxia (<0.1% oxygen), where the latter is often confused with physiological hypoxia, are capable of inducing a HIF-independent autophagic response, generated via an extreme nutritional stress response implicating the AMPK-mTOR and unfolded protein response (UPR) pathways. The autophagic cell death that is often observed in these extreme stress conditions should be seen as the outcome of failed adaptation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Cell Hypoxia
  • Cell Survival
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Membrane Proteins / metabolism
  • Models, Biological


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins