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Updated: Sep 6, 2025

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

10.9K

The web of death: the expanding complexity of necroptotic signaling

Christopher R Horne1, André L Samson1, James M Murphy1

  • 1Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Trends in Cell Biology
|June 24, 2022
PubMed

Insights

Necroptosis, a programmed cell death pathway, is increasingly linked to diseases. Core components like RIPK1, RIPK3, and MLKL interact with other proteins, creating complex regulatory networks that vary across species.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Immunology

Background:

  • Necroptosis is a programmed cell death pathway implicated in various diseases.
  • Receptor interacting protein kinase (RIPK)1 and RIPK3, and mixed lineage kinase domain-like (MLKL) form the core of this pathway.
  • Pathway regulation is complex, involving protein interactions and post-translational modifications.

Purpose of the Study:

  • To elucidate the network of proteins regulating necroptosis.
  • To explore the evolutionary divergence of necroptosis components across species.

Main Methods:

  • Review of current literature on necroptosis signaling.
  • Comparative analysis of RIPK3-MLKL interactions and regulation.

Main Results:

  • Identification of a complex web of protein interactions that modulate necroptotic signaling.
  • Evidence of species-specific adaptations in necroptosis pathway components, particularly RIPK3-MLKL.

Conclusions:

  • The necroptosis pathway is finely tuned by a diverse set of protein interactions.
  • Evolutionary pressures, likely from pathogens, have shaped the divergence of necroptosis signaling, especially the RIPK3-MLKL axis.
Keywords:
lyticphosphorylationprogrammed cell deathprogrammed necrosispseudokinase

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