title: Cell death induced by endoplasmic reticulum stress.
abstract: The endoplasmic reticulum is an organelle with multiple functions. The synthesis of transmembrane proteins and proteins that are to be secreted occurs in this organelle. Many conditions that impose stress on cells, including hypoxia, starvation, infections and changes in secretory needs, challenge the folding capacity of the cell and promote endoplasmic reticulum stress. The cellular response involves the activation of sensors that transduce signaling cascades with the aim of restoring homeostasis. This is known as the unfolded protein response, which also intersects with the integrated stress response that reduces protein synthesis through inactivation of the initiation factor eIF2α. Central to the unfolded protein response are the sensors PERK, IRE1 and ATF6, as well as other signaling nodes such as c-Jun N-terminal kinase 1 (JNK) and the downstream transcription factors XBP1, ATF4 and CHOP. These proteins aim to restore homeostasis, but they can also induce cell death, which has been shown to occur by necroptosis and, more commonly, through the regulation of Bcl-2 family proteins (Bim, Noxa and Puma) that leads to mitochondrial apoptosis. In addition, endoplasmic reticulum stress and proteotoxic stress have been shown to induce TRAIL receptors and activation of caspase-8. Endoplasmic reticulum stress is a common feature in the pathology of numerous diseases because it plays a role in neurodegeneration, stroke, cancer, metabolic diseases and inflammation. Understanding how cells react to endoplasmic reticulum stress can accelerate discovery of drugs against these diseases.
authors.affiliation: Cell Death Regulation Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Iurlaro
authors.affiliation: Cell Death Regulation Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Muñoz-Pinedo
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009336:Necrosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D053181:Caspase 8; D004722:Endoribonucleases; D017346:Protein Serine-Threonine Kinases; D053218:Receptors, Death Domain; D019892:eIF-2 Kinase; C528229:ERN1 protein, human
keywords: Bcl-2 family proteins; apoptosis; autophagy; caspase-8; cell death; death receptors; endoplasmic reticulum stress; iDISC; mitochondrial pathway; necrosis