title: Hypoxia-induced autophagy: cell death or cell survival?
abstract: 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.
authors.affiliation: 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
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Mazure
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
mesh_terms: 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
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins