Molecular mechanisms of necroptosis: an ordered cellular explosion

Nat Rev Mol Cell Biol. 2010 Oct;11(10):700-14. doi: 10.1038/nrm2970. Epub 2010 Sep 8.


For a long time, apoptosis was considered the sole form of programmed cell death during development, homeostasis and disease, whereas necrosis was regarded as an unregulated and uncontrollable process. Evidence now reveals that necrosis can also occur in a regulated manner. The initiation of programmed necrosis, 'necroptosis', by death receptors (such as tumour necrosis factor receptor 1) requires the kinase activity of receptor-interacting protein 1 (RIP1; also known as RIPK1) and RIP3 (also known as RIPK3), and its execution involves the active disintegration of mitochondrial, lysosomal and plasma membranes. Necroptosis participates in the pathogenesis of diseases, including ischaemic injury, neurodegeneration and viral infection, thereby representing an attractive target for the avoidance of unwarranted cell death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Death / physiology*
  • Cell Membrane / pathology
  • Cell Membrane / physiology
  • Humans
  • Lysosomes / pathology
  • Lysosomes / physiology
  • Macrophages / microbiology
  • Macrophages / pathology
  • Mitochondria / pathology
  • Mitochondria / physiology
  • Morphogenesis / physiology
  • Necrosis
  • Protein Kinases / metabolism
  • Receptors, Death Domain / physiology*
  • Receptors, Tumor Necrosis Factor, Type I / physiology
  • Shigella flexneri / pathogenicity


  • Receptors, Death Domain
  • Receptors, Tumor Necrosis Factor, Type I
  • Protein Kinases