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Cold Spring Harb Perspect Biol. 2012 Nov 1;4(11). pii: a008805. doi: 10.1101/cshperspect.a008805.

Fueling the flames: Mammalian programmed necrosis in inflammatory diseases.

Author information

  • 1Department of Pathology, Immunology and Virology Program, University of Massachusetts Medical School, Worcester, 01655, USA. francis.chan@umassmed.edu

Abstract

Programmed necrosis or necroptosis is an inflammatory form of cell death driven by TNF-like death cytokines, toll-like receptors, and antigen receptors. Unlike necrosis induced by physical trauma, a dedicated pathway is involved in programmed necrosis. In particular, a kinase complex composed of the receptor interacting protein kinase 1 (RIPK1) and RIPK3 is a central step in necrotic cell death. Assembly and activation of this RIPK1-RIPK3 "necrosome" is critically controlled by protein ubiquitination, phosphorylation, and caspase-mediated cleavage events. The molecular signals cumulate in formation of intracellular vacuoles, organelle swelling, internal membrane leakage, and eventually plasma membrane rupture. These morphological changes can result in spillage of intracellular adjuvants to promote inflammation and further exacerbate tissue injury. Because of the inflammatory nature of necrosis, it is an attractive pathway for therapeutic intervention in acute inflammatory diseases.

PMID:
23125016
[PubMed - indexed for MEDLINE]
PMCID:
PMC3536335
Free PMC Article
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