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

Hypoxia-induced autophagy: cell death or cell survival?

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  • 1Institute of Developmental Biology and Cancer Research, University of Nice, CNRS-UMR 6543, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France.


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.

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