title: The role of necroptosis in pulmonary diseases.
abstract: By regulating the cell number and eliminating harmful cells, programmed cell death plays a critical role in development, homeostasis, and disease. While apoptosis is a recognized form of programmed cell death, necrosis was considered a type of uncontrolled cell death induced by extreme physical or chemical stress. However, recent studies have revealed the existence of a genetically programmed and regulated form of necrosis, termed necroptosis. Necroptosis is defined as necrotic cell death that is dependent on receptor-interacting protein kinase 3 (RIPK3). RIPK3, receptor-interacting protein kinase 1 (RIPK1), and a mixed-lineage kinase domain-like protein (MLKL) form a multiprotein complex called a necrosome. Although necroptosis generally provides a cell-autonomous host defense, on the other hand, cell rupture caused by necroptosis induces inflammation through the release of damage-associated molecular patterns, such as mitochondrial DNA, HMGB1, and IL-1. Previously, necroptosis was considered an alternative to apoptosis, but it is becoming increasingly clear that necroptosis itself is relevant to clinical disease, independent of apoptosis. According to some recent studies, autophagy, a cellular process for organelle and protein turnover, regulates necroptosis. This review outlines the principal components of necroptosis and provides an overview of the emerging importance of necroptosis in the pathogenesis of pulmonary disease, including chronic obstructive pulmonary disease, lung cancer, infection, and sepsis. We also discuss the molecular relationship between necroptosis and autophagy. Strategies targeting necroptosis may yield novel therapies for pulmonary diseases.
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: mizumura.kenji@nihon-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mizumura
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: maruoka.shuichiro@nihon-u.ac.jp.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Maruoka
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: gon.yasuhiro@nihon-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Gon
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA. Electronic address: amc2056@med.cornell.edu.
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: hashimoto.shu@nihon-u.ac.jp.
authors.forename: Shu
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D001343:Autophagy / Q000502:physiology; D016923:Cell Death / Q000235:genetics*; D004272:DNA, Mitochondrial; D024243:HMGB1 Protein; D007375:Interleukin-1; D008175:Lung Neoplasms / Q000209:etiology* / Q000628:therapy; D046912:Multiprotein Complexes; D009336:Necrosis; D011494:Protein Kinases / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000628:therapy; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D007375:Interleukin-1; D046912:Multiprotein Complexes; C570693:MLKL protein, human; D011494:Protein Kinases; C506249:RIPK1 protein, human; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: Autophagy; Chronic obstructive pulmonary disease; Mitophagy; Necroptosis