title: Necroptosis: Mechanisms and Relevance to Disease.
abstract: Necroptosis is a form of regulated cell death that critically depends on receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) and generally manifests with morphological features of necrosis. The molecular mechanisms that underlie distinct instances of necroptosis have just begun to emerge. Nonetheless, it has already been shown that necroptosis contributes to cellular demise in various pathophysiological conditions, including viral infection, acute kidney injury, and cardiac ischemia/reperfusion. Moreover, human tumors appear to obtain an advantage from the downregulation of key components of the molecular machinery for necroptosis. Although such an advantage may stem from an increased resistance to adverse microenvironmental conditions, accumulating evidence indicates that necroptosis-deficient cancer cells are poorly immunogenic and hence escape natural and therapy-elicited immunosurveillance. Here, we discuss the molecular mechanisms and relevance to disease of necroptosis.
authors.affiliation: Department of Radiation Oncology, Weill Cornell Medical College, New York, NY 10065; email: deadoc@vodafone.it.|Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; email: kroemer@orange.fr.|INSERM, U1138, 75006 Paris, France.|Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France.|Université Pierre et Marie Curie/Paris VI, 75006 Paris, France.|Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.affiliation: Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; email: kroemer@orange.fr.|INSERM, U1138, 75006 Paris, France.|Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France.|Université Pierre et Marie Curie/Paris VI, 75006 Paris, France.|Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; email: captain.olsen@gmail.com.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.affiliation: University of Massachusetts Medical School, Worcester, Massachusetts 01065; email: francis.chan@umassmed.edu.
authors.forename: Francis Ka-Ming
authors.initials: FK
authors.lastname: Chan
authors.affiliation: Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; email: kroemer@orange.fr.|INSERM, U1138, 75006 Paris, France.|Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France.|Université Pierre et Marie Curie/Paris VI, 75006 Paris, France.|Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; email: captain.olsen@gmail.com.|Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, 17176 Stockholm, Sweden.|Pôle de Biologie, Hôpital Européen George Pompidou, AP-HP, 75015 Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D017209:Apoptosis; D004194:Disease; D006801:Humans; D009336:Necrosis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: caspases; damage-associated molecular patterns; immunogenic cell death; inflammation; mitochondrial permeability transition; necrostatin-1