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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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Post-translational control of RIPK3 and MLKL mediated necroptotic cell death

James M Murphy1,2, James E Vince1,2

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

F1000Research
|May 10, 2016
PubMed

Insights

Programmed cell death, including necroptosis (receptor interacting protein kinase-3/mixed lineage kinase domain-like pathway), is crucial for host defense but can be pathological. This review details post-translational regulation of necroptosis signaling.

Area of Science:

  • Cellular biology
  • Immunology
  • Molecular mechanisms of cell death

Background:

  • Programmed cell death pathways, such as necroptosis, are increasingly recognized for their roles in immunity and disease.
  • The receptor interacting protein kinase-3 (RIPK3)-mixed lineage kinase domain-like (MLKL) pathway is a key necroptotic signaling cascade.
  • Dysregulation of necroptosis is implicated in autoimmune and autoinflammatory conditions.

Purpose of the Study:

  • To review recent advances in understanding the post-translational control of RIPK3-MLKL necroptotic signaling.
  • To elucidate the regulatory roles of phosphorylation, ubiquitination, and deubiquitination in necroptosis.
  • To discuss the mechanisms by which MLKL induces cell membrane disruption.

Main Methods:

  • Literature review of recent research on necroptosis signaling.
  • Analysis of genetic studies on the role of programmed necrosis in host resistance.
  • Discussion of biochemical and molecular mechanisms regulating RIPK3-MLKL pathway.

Main Results:

  • Phosphorylation is critical for the execution of necroptosis.
  • Ubiquitin ligases and deubiquitinating enzymes emerge as key regulators of necroptosis.
  • MLKL is identified as the terminal effector triggering cell lysis.

Conclusions:

  • Post-translational modifications, particularly phosphorylation and ubiquitination, finely tune necroptosis.
  • Understanding necroptosis regulation is vital for addressing its role in infection and inflammatory diseases.
  • MLKL's membrane-disrupting function is central to necroptotic cell death.
Keywords:
MLKLRIPK3mixed lineage kinase domain-likenecroptosisnecroptotic cell deathreceptor interacting protein kinase-3

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