{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Du G"],"funding":["NICHD NIH HHS","NCCIH NIH HHS","NIDDK NIH HHS","NIAID NIH HHS","NHLBI NIH HHS","NCI NIH HHS"],"pagination":["437-446"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11283288"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["630(8016)"],"pubmed_abstract":["Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores after cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT)<sup>1-10</sup>. Here we report that GSDMD Cys191 is S-palmitoylated and that palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS). Cleavage-deficient GSDMD (D275A) is also palmitoylated after inflammasome stimulation or treatment with ROS activators and causes pyroptosis, although less efficiently than palmitoylated GSDMD-NT. Palmitoylated, but not unpalmitoylated, full-length GSDMD induces liposome leakage a"],"journal":["Nature"],"pubmed_title":["ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D."],"pmcid":["PMC11283288"],"funding_grant_id":["R01 AI124491","R01 AI182369","R37 AI116550","R01 AI139914","P01 HL158688","R01 CA240955","P30 DK034854","DP1 HD087988","R01 AT010268","R01 AI116550","R01 AI167993"],"pubmed_authors":["El-Baba TJ","Dong Y","Lutomski CA","Miao R","Ma X","Devant P","Robinson CV","Banerjee A","Wu H","Luo HR","Gu B","Puthenveetil R","Oh SF","Pi X","Balasubramanian A","Fontana P","Du G","Walker C","Kagan JC","Healy LB","David L","Goh B","Lieberman J"],"additional_accession":[]},"is_claimable":false,"name":"ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D.","description":"Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores after cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT)<sup>1-10</sup>. Here we report that GSDMD Cys191 is S-palmitoylated and that palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS). Cleavage-deficient GSDMD (D275A) is also palmitoylated after inflammasome stimulation or treatment with ROS activators and causes pyroptosis, although less efficiently than palmitoylated GSDMD-NT. Palmitoylated, but not unpalmitoylated, full-length GSDMD induces liposome leakage a","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-06-03T05:28:30.79Z","creation":"2025-04-06T22:24:32.778Z"},"accession":"S-EPMC11283288","cross_references":{"pubmed":["38599239"],"doi":["10.1038/s41586-024-07373-5"]}}