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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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Necroptosis in development and diseases

Bing Shan1, Heling Pan1, Ayaz Najafov2

  • 1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, PuDong District, Shanghai 201203, China.

Genes & Development
|March 30, 2018
PubMed

Insights

Necroptosis, a regulated cell death pathway involving RIPK1, RIPK3, and MLKL, can occur when apoptosis is blocked. Inhibiting RIPK1 offers a therapeutic strategy for diseases involving both cell death types.

Area of Science:

  • Cellular biology
  • Immunology
  • Molecular mechanisms of cell death

Background:

  • Necroptosis is a regulated necrotic cell death pathway.
  • It is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like pseudokinase (MLKL).
  • Necroptosis can be activated under conditions where apoptosis is deficient.

Purpose of the Study:

  • To investigate the role of RIPK1 in regulating necroptosis and apoptosis.
  • To explore the therapeutic potential of RIPK1 inhibition in disease.

Main Methods:

  • Analysis of mutant mice deficient in RIPK1, RIPK3, or MLKL.
  • Investigation of cellular responses under apoptosis-deficient conditions.
  • Evaluation of RIPK1 inhibition as a therapeutic strategy.

Main Results:

  • Mutant mice lacking kinase-dead RIPK1, RIPK3, or MLKL exhibit normal development and homeostasis.
  • Necroptosis and apoptosis are activated in response to mutations causing embryonic abortion.
  • These cell death pathways are implicated in human inflammatory and neurodegenerative diseases.

Conclusions:

  • Modulating RIPK1 activity through ubiquitination and phosphorylation is crucial for controlling necroptosis and apoptosis.
  • RIPK1 inhibition is a promising therapeutic approach for diseases benefiting from the blockade of both necroptosis and apoptosis.
Keywords:
MLKLRIPK1RIPK3apoptosisnecroptosis

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