Related Experiment Video

Updated: Jul 1, 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

Gasdermin and MLKL necrotic cell death effectors: Signaling and diseases

Kate E Lawlor1, James M Murphy2, James E Vince3

  • 1Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia; Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia.

Immunity
|March 13, 2024
PubMed

Insights

Necrotic cell death, involving MLKL and gasdermin proteins, can trigger inflammation in various diseases. Understanding these cell death pathways is crucial for developing new treatments for inflammatory conditions.

Area of Science:

  • Cellular Biology
  • Immunology
  • Pathology

Background:

  • Inflammatory conditions are linked to cellular damage and death.
  • Apoptotic cell death is anti-inflammatory, while necroptosis and pyroptosis are inflammatory.
  • MLKL and gasdermin proteins drive membrane damage in necrotic cell death.

Purpose of the Study:

  • To review the function and regulation of MLKL and gasdermin.
  • To evaluate the role of MLKL- and gasdermin-driven necrosis in disease.
  • To highlight the need for research on pyroptosis and necroptosis in human tissues.

Main Methods:

  • Literature review of inflammatory conditions.
  • Analysis of genetic evidence from gene-targeted mice studies.
  • Evaluation of MLKL and gasdermin effector proteins.

Main Results:

  • Necroptosis (MLKL) and pyroptosis (gasdermin) drive inflammatory responses.
  • MLKL and gasdermin-driven necrosis can be protective or detrimental in disease.
  • Gene-targeted mice studies provide insights into these pathways.

Conclusions:

  • MLKL and gasdermin are key effectors of inflammatory necrotic cell death.
  • The role of necroptosis and pyroptosis in disease is context-dependent.
  • Further research in human tissues is needed to develop targeted necrotic inhibitors for inflammatory diseases.
Keywords:
GSDMDGSDMEMLKLNINJ1RIPK3caspase-1gasdermininflammasomenecroptosispyroptosis

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