A palmitoylation–depalmitoylation relay spatiotemporally controls GSDMD activation in pyroptosis

Broz, P., Pelegrin, P. & Shao, F. The gasdermins, a protein family executing cell death and inflammation. Nat. Rev. Immunol. 20, 143–157 (2020).

Article  CAS  PubMed  Google Scholar 

Hou, J., Hsu, J. M. & Hung, M. C. Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity. Mol. Cell 81, 4579–4590 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi, J. et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660–665 (2015).

Article  CAS  PubMed  Google Scholar 

He, W. T. et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res. 25, 1285–1298 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666–671 (2015).

Article  CAS  PubMed  Google Scholar 

Xia, S. et al. Gasdermin D pore structure reveals preferential release of mature interleukin-1. Nature 593, 607–611 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Orning, P. et al. Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science 362, 1064–1069 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarhan, J. et al. Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection. Proc. Natl Acad. Sci. USA 115, E10888–E10897 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Humphries, F. et al. Succination inactivates gasdermin D and blocks pyroptosis. Science 369, 1633–1637 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang, X. et al. NU6300 covalently reacts with cysteine-191 of gasdermin D to block its cleavage and palmitoylation. Sci. Adv. 10, eadi9284 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Evavold, C. L. et al. Control of gasdermin D oligomerization and pyroptosis by the Ragulator–Rag–mTORC1 pathway. Cell 184, 4495–4511 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Devant, P. et al. Gasdermin D pore-forming activity is redox-sensitive. Cell Rep. 42, 112008 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, X. et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535, 153–158 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sborgi, L. et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 35, 1766–1778 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, K. et al. Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis. Cell 180, 941–955 (2020).

Article  CAS  PubMed  Google Scholar 

Liu, Z. et al. Caspase-1 engages full-length gasdermin D through two distinct interfaces that mediate caspase recruitment and substrate cleavage. Immunity 53, 106–114 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Linder, M. E. & Deschenes, R. J. Palmitoylation: policing protein stability and traffic. Nat. Rev. Mol. Cell Biol. 8, 74–84 (2007).

Article  CAS  PubMed  Google Scholar 

Main, A. & Fuller, W. Protein S-palmitoylation: advances and challenges in studying a therapeutically important lipid modification. FEBS J. 289, 861–882 (2022).

Article  CAS  PubMed  Google Scholar 

Greaves, J. & Chamberlain, L. H. DHHC palmitoyl transferases: substrate interactions and (patho)physiology. Trends Biochem. Sci. 36, 245–253 (2011).

Article  CAS  PubMed  Google Scholar 

Fukata, Y. & Fukata, M. Protein palmitoylation in neuronal development and synaptic plasticity. Nat. Rev. Neurosci. 11, 161–175 (2010).

Article  CAS  PubMed  Google Scholar 

Zhang, Y., Qin, Z., Sun, W., Chu, F. & Zhou, F. Function of protein S-palmitoylation in immunity and immune-related diseases. Front. Immunol. 12, 661202 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, B., Sun, Y., Niu, J., Jarugumilli, G. K. & Wu, X. Protein lipidation in cell signaling and diseases: function, regulation, and therapeutic opportunities. Cell Chem. Biol. 25, 817–831 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Akimzhanov, A. M. & Boehning, D. Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling. Proc. Natl Acad. Sci. USA 112, 11876–11880 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mukai, K. et al. Activation of STING requires palmitoylation at the Golgi. Nat. Commun. 7, 11932 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, M. et al. A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis. Nature 586, 434–439 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morrison, E. et al. Dynamic palmitoylation events following T-cell receptor signaling. Commun. Biol. 3, 368 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hao, J. W. et al. CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis. Nat. Commun. 11, 4765 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hu, L. et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate. Cell Death Dis. 11, 281 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhuang, Z., Gu, J., Li, B. O. & Yang, L. Inhibition of gasdermin D palmitoylation by disulfiram is crucial for the treatment of myocardial infarction. Transl. Res. 264, 66–75 (2023).

Article  PubMed  Google Scholar 

Johnson, A. G. et al. Bacterial gasdermins reveal an ancient mechanism of cell death. Science 375, 221–225 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sobocinska, J. et al. Lipopolysaccharide upregulates palmitoylated enzymes of the phosphatidylinositol cycle: an insight from proteomic studies. Mol. Cell. Proteom. 17, 233–254 (2018).

Article  CAS  Google Scholar 

Martin, B. R. & Cravatt, B. F. Large-scale profiling of protein palmitoylation in mammalian cells. Nat. Methods 6, 135–138 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martin, B. R. Nonradioactive analysis of dynamic protein palmitoylation. Curr. Protoc. Protein Sci. 73, 14.15.1–14.15.9 (2013).

Article  PubMed  Google Scholar 

Lu, Y. et al. Palmitoylation of NOD1 and NOD2 is required for bacterial sensing. Science 366, 460–467 (2019).

Article  CAS  PubMed  Google Scholar 

Webb, Y., Hermida-Matsumoto, L. & Resh, M. D. Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids. J. Biol. Chem. 275, 261–270 (2000).

Article  CAS  PubMed  Google Scholar 

Hannoush, R. N. & Sun, J. The chemical toolbox for monitoring protein fatty acylation and prenylation. Nat. Chem. Biol. 6, 498–506 (2010).

Article  CAS  PubMed 

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