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Annu Rev Pathol. 2017 Jan 24;12:103-130. doi: 10.1146/annurev-pathol-052016-100247. Epub 2016 Dec 5.

Necroptosis: Mechanisms and Relevance to Disease.

Galluzzi L1,2,3,4,5,6, Kepp O2,3,4,5,7, Chan FK8, Kroemer G2,3,4,5,7,9,10.

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Department of Radiation Oncology, Weill Cornell Medical College, New York, NY 10065; email:
Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; email:
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.
Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; email:
University of Massachusetts Medical School, Worcester, Massachusetts 01065; email:
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.


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.


caspases; damage-associated molecular patterns; immunogenic cell death; inflammation; mitochondrial permeability transition; necrostatin-1

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