Regulated necrosis: the expanding network of non-apoptotic cell death pathways

Nat Rev Mol Cell Biol. 2014 Feb;15(2):135-47. doi: 10.1038/nrm3737.

Abstract

Cell death research was revitalized by the understanding that necrosis can occur in a highly regulated and genetically controlled manner. Although RIPK1 (receptor-interacting protein kinase 1)- and RIPK3-MLKL (mixed lineage kinase domain-like)-mediated necroptosis is the most understood form of regulated necrosis, other examples of this process are emerging, including cell death mechanisms known as parthanatos, oxytosis, ferroptosis, NETosis, pyronecrosis and pyroptosis. Elucidating how these pathways of regulated necrosis are interconnected at the molecular level should enable this process to be therapeutically targeted.

Publication types

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

MeSH terms

  • Apoptosis / genetics*
  • Cell Death / genetics
  • Humans
  • Molecular Targeted Therapy*
  • Necrosis / genetics*
  • Necrosis / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction*

Substances

  • MLKL protein, human
  • Protein Kinases
  • RIPK1 protein, human
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases