title: When ER stress reaches a dead end.
abstract: Endoplasmic reticulum (ER) stress is a common feature of several physiological and pathological conditions affecting the function of the secretory pathway. To restore ER homeostasis, an orchestrated signaling pathway is engaged that is known as the unfolded protein response (UPR). The UPR has a primary function in stress adaptation and cell survival; however, under irreversible ER stress a switch to pro-apoptotic signaling events induces apoptosis of damaged cells. The mechanisms that initiate ER stress-dependent apoptosis are not fully understood. Several pathways have been described where we highlight the participation of the BCL-2 family of proteins and ER calcium release. In addition, recent findings also suggest that microRNAs and oxidative stress are relevant players on the transition from adaptive to cell death programs. Here we provide a global and integrated overview of the signaling networks that may determine the elimination of a cell under chronic ER stress. This article is part of a Special Section entitled: Cell Death Pathways.
authors.affiliation: Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Hery
authors.initials: H
authors.lastname: Urra
authors.affiliation: Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Estefanie
authors.initials: E
authors.lastname: Dufey
authors.affiliation: Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Lisbona
authors.affiliation: Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Diego
authors.initials: D
authors.lastname: Rojas-Rivera
authors.affiliation: Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA; Neurounion Biomedical Foundation, Santiago, Chile. Electronic address: chetz@med.uchile.cl.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
mesh_terms: D000818:Animals; D016923:Cell Death; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D008954:Models, Biological; D056811:Unfolded Protein Response
keywords: Adaptation; Apoptosis; Cell death; ER stress; Unfolded protein response