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Death Receptor-induced Necroptosis

  1. Wim Declercq,
  2. Franky Van Herreweghe,
  3. Tom Vanden Berghe,
  4. Peter Vandenabeele

Published Online: 15 DEC 2009

DOI: 10.1002/9780470015902.a0021566

eLS

eLS

How to Cite

Declercq, W., Van Herreweghe, F., Berghe, T. V. and Vandenabeele, P. 2009. Death Receptor-induced Necroptosis. eLS. .

Author Information

  1. VIB-Ghent University, Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, Ghent, Belgium

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Recent studies on cellular in vitro models have made it clear that death receptor (DR)-induced necrosis, also called necroptosis, is a programmed form of necrotic cell death. In contrast, accidental necrosis is mainly induced by physicochemical stress, such as heath or chemicals. Many DRs signal to apoptosis or necroptosis depending on whether caspases are active or not. The kinase activities of receptor-interacting protein 1 (RIP1) and RIP3 have emerged as crucial regulators of DR-induced necroptosis. The precise execution mechanisms during necroptosis are still poorly understood but involve different cellular compartments such as the mitochondria, the lysosomes and the cell membrane. In vivo, necroptosis occurs mainly in pathophysiological processes such as ischaemia-reperfusion injury in heart, brain and kidneys, viral infection and pancreatitis, and is capable of killing tumour cells that have developed strategies to evade apoptosis. Thus, detailed knowledge of necroptotic signalling may be exploited in therapeutic strategies.

Key concepts:

  • Necrosis is characterized by swelling of the endoplasmic reticulum, mitochondria and cytoplasm, with subsequent rupture of the plasma membrane and lysis of the cells.

  • Death receptor-induced necrosis, also called necroptosis, is a programmed form of necrotic cell death. This is in contrast to necrosis induced by physicochemical stress, such as heath or hydrogen peroxide.

  • The necrosis-signalling complex, or necrosome, consists of a complex containing FADD, caspase-8, RIP1 and RIP3.

  • Expression of RIP3 renders cells permissive to death receptor-induced necroptosis.

  • RIP1 and RIP3 kinase activity is crucial for necroptotic signalling.

  • Apoptosis counteracts necrotic signalling by cleavage of RIP1 and RIP3.

  • Necroptosis forms a back-up cell death mode in case caspases activity is prevented or inhibited.

  • In vivo, necroptosis occurs mainly in pathophysiological processes such as ischaemia-reperfusion injury in heart, brain and kidneys, viral infection and pancreatitis, and is capable of killing tumour cells that have developed strategies to evade apoptosis.

Keywords:

  • necrosis–death receptors;
  • TNF-necrosome;
  • receptor-interacting kinase;
  • mitochondria-reactive oxygen species;
  • metabolism