Fueling the flames: Mammalian programmed necrosis in inflammatory diseases.

Published online

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Chan, FK-M

Published Date

  • November 1, 2012

Published In

Volume / Issue

  • 4 / 11

PubMed ID

  • 23125016

Pubmed Central ID

  • 23125016

Electronic International Standard Serial Number (EISSN)

  • 1943-0264

Digital Object Identifier (DOI)

  • 10.1101/cshperspect.a008805

Language

  • eng

Conference Location

  • United States