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Updated: Feb 11, 2026

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma

Nathalia M de Vasconcelos1,2, Nina Van Opdenbosch1,2, Hanne Van Gorp1,2

  • 1Department of Internal Medicine, Ghent University, Ghent, B-9000, Belgium.

Cell Death and Differentiation
|April 19, 2018
PubMed

Insights

Pyroptosis, a cell death mechanism, involves gasdermin D (GSDMD) pores that cause cell swelling and rupture. This study models the precise subcellular events leading to pyroptotic cell disintegration.

Area of Science:

  • Cellular Biology
  • Immunology
  • Pathology

Background:

  • Pyroptosis is an inflammatory cell death mechanism crucial for antimicrobial defense and linked to autoinflammatory diseases.
  • It is triggered by caspases, leading to gasdermin D (GSDMD) cleavage and plasma membrane perforation.
  • Subcellular events preceding pyroptotic lysis remain poorly understood.

Purpose of the Study:

  • To elucidate the dynamic subcellular events preceding pyroptotic cell lysis.
  • To propose a refined model of pyroptotic cell disintegration based on single-cell dynamics.
  • To chronologically map gasdermin D (GSDMD)-mediated events in pyroptosis.

Main Methods:

  • Primary macrophages were induced into pyroptosis via three inflammasome types.
  • High-resolution live-cell spinning disk confocal laser microscopy was employed.
  • Quantitative analysis of single-cell subcellular events was performed.

Main Results:

  • A model of pyroptotic cell disintegration was proposed, initiated by GSDMD-dependent ion channels.
  • These channels are more restrictive than previously suggested GSDMD pores.
  • Events include osmotic swelling, organelle commitment, and eventual plasma membrane rupture.

Conclusions:

  • This study provides a dynamic framework for understanding pyroptosis.
  • A chronological sequence of GSDMD-mediated subcellular events in pyroptosis was established.
  • The findings clarify the cellular disintegration process during pyroptotic cell death.

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