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Gasdermin D triggers cardiolipin-driven mitochondrial damage and pyroptosis

Qiang Cai1, Quazi T H Shubhra2

  • 1Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Trends in Immunology
|January 19, 2024
PubMed

Insights

Gasdermin D N-terminal (GSDMD-NT) causes mitochondrial damage during pyroptosis by creating pores in mitochondrial membranes. Mitochondrial cardiolipin is crucial for GSDMD-NT

Area of Science:

  • Cellular Biology
  • Immunology
  • Biochemistry

Background:

  • Pyroptosis is a pro-inflammatory programmed cell death pathway.
  • Gasdermin D (GSDMD) is a key executioner protein in pyroptosis.
  • The precise mechanisms of GSDMD-mediated cell damage are under investigation.

Purpose of the Study:

  • To elucidate the role of gasdermin D N-terminal (GSDMD-NT) in pyroptosis-induced mitochondrial damage.
  • To identify key molecular players involved in GSDMD-NT's mitochondrial effects.

Main Methods:

  • Investigated the interaction of GSDMD-NT with mitochondrial membranes.
  • Utilized biochemical assays to assess pore formation and cardiolipin binding.
  • Examined mitochondrial integrity following GSDMD-NT activation.

Main Results:

  • Gasdermin D N-terminal (GSDMD-NT) directly induces mitochondrial damage.
  • GSDMD-NT forms pores in both the inner and outer mitochondrial membranes (OMMs).
  • Mitochondrial cardiolipin is essential for GSDMD-NT's pore-forming activity and subsequent damage.

Conclusions:

  • GSDMD-NT is a direct instigator of mitochondrial damage during pyroptosis.
  • The findings reveal a novel mechanism of pyroptosis involving direct mitochondrial membrane permeabilization.
  • Highlights the critical role of cardiolipin in GSDMD-mediated inflammatory cell death.
Keywords:
cardiolipingasdermin Dmitochondriapyroptosisreactive oxygen species

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