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Updated: Apr 14, 2026
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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
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Dynamic S-Acylation of GSDMA Regulates Pyroptosis.
Zhipeng Tao1,2, Ritesh P Thakare3, Melyssa Cheung4,5
1Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
ACS Chemical Biology
|April 13, 2026
Summary
Gasdermin A (GSDMA) undergoes S-acylation, a lipid modification promoting pyroptosis by aiding membrane anchoring and oligomerization. This mechanism differs from GSDMD palmitoylation and involves ABHD17A regulation.
Area of Science:
- Cellular biology
- Immunology
- Molecular mechanisms of cell death
Background:
- Gasdermin A (GSDMA) is crucial for pyroptosis during infection.
- GSDMD is known to undergo palmitoylation, but lipid modifications of other gasdermins are unclear.
Purpose of the Study:
- To investigate lipid modifications of GSDMA.
- To elucidate the functional consequences of GSDMA S-acylation.
Main Methods:
- Biochemical assays to detect S-acylation.
- In vitro studies with recombinant proteins.
- Identification of deacylating enzymes.
Main Results:
- GSDMA is S-acylated at conserved N-terminal cysteine residues.
- S-acylation enhances GSDMA membrane anchoring and oligomerization, promoting pyroptosis.
- GSDMA and GSDMD can be S-acylated in vitro via direct interaction with palmitoyl-CoA.
- ABHD17A identified as a deacylating enzyme regulating GSDMA.
Conclusions:
- GSDMA S-acylation is a novel mechanism promoting pyroptosis, distinct from GSDMD palmitoylation.
- Lipid modification plays a key role in regulating GSDMA function during pyroptosis.
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