Hypoxia-induced autophagy: cell death or cell survival?
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.
Mazure
Nathalie M
NM
Institute of Developmental Biology and Cancer Research, University of Nice, CNRS-UMR 6543, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France. mazure@unice.fr
Pouysségur
Jacques
J
D000818:Animals; D001343:Autophagy; D015687:Cell Hypoxia; D002470:Cell Survival; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins