Molecular mechanisms of gasdermin D pore-forming activity.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
22
02
2023
accepted:
03
05
2023
medline:
30
6
2023
pubmed:
6
6
2023
entrez:
5
6
2023
Statut:
ppublish
Résumé
The regulated disruption of the plasma membrane, which can promote cell death, cytokine secretion or both is central to organismal health. The protein gasdermin D (GSDMD) is a key player in this process. GSDMD forms membrane pores that can promote cytolysis and the release of interleukin-1 family cytokines into the extracellular space. Recent discoveries have revealed biochemical and cell biological mechanisms that control GSDMD pore-forming activity and its diverse downstream immunological effects. Here, we review these multifaceted regulatory activities, including mechanisms of GSDMD activation by proteolytic cleavage, dynamics of pore assembly, regulation of GSDMD activities by posttranslational modifications, membrane repair and the interplay of GSDMD and mitochondria. We also address recent insights into the evolution of the gasdermin family and their activities in species across the kingdoms of life. In doing so, we hope to condense recent progress and inform future studies in this rapidly moving field in immunology.
Identifiants
pubmed: 37277654
doi: 10.1038/s41590-023-01526-w
pii: 10.1038/s41590-023-01526-w
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Gasdermins
0
Interleukin-1
0
Inflammasomes
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1064-1075Informations de copyright
© 2023. Springer Nature America, Inc.
Références
Shi, J. et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660–665 (2015).
pubmed: 26375003
doi: 10.1038/nature15514
Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666–671 (2015).
pubmed: 26375259
doi: 10.1038/nature15541
He, W. et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res. 25, 1285–1298 (2015).
pubmed: 26611636
pmcid: 4670995
doi: 10.1038/cr.2015.139
Liu, X. et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 535, 153–158 (2016).
pubmed: 27383986
pmcid: 5539988
doi: 10.1038/nature18629
Aglietti, R. A. et al. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. Proc. Natl Acad. Sci. USA 113, 7858–7863 (2016).
pubmed: 27339137
pmcid: 4948338
doi: 10.1073/pnas.1607769113
Sborgi, L. et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 35, 1766–1778 (2016).
pubmed: 27418190
pmcid: 5010048
doi: 10.15252/embj.201694696
Ding, J. et al. Pore-forming activity and structural auto-inhibition of the gasdermin family. Nature 535, 111–116 (2016).
pubmed: 27281216
doi: 10.1038/nature18590
Evavold, C. L. et al. The pore-forming protein gasdermin D regulates interleukin-1 secretion from living macrophages. Immunity 48, 35–44 (2018).
pubmed: 29195811
doi: 10.1016/j.immuni.2017.11.013
Heilig, R. et al. The gasdermin-D pore acts as a conduit for IL-1β secretion in mice. Eur. J. Immunol. 48, 584–592 (2018).
pubmed: 29274245
doi: 10.1002/eji.201747404
Orning, P., Lien, E. & Fitzgerald, K. A. Gasdermins and their role in immunity and inflammation. J. Exp. Med. 216, 2453–2465 (2019).
pubmed: 31548300
pmcid: 6829603
doi: 10.1084/jem.20190545
Vora, S. M., Lieberman, J. & Wu, H. Inflammasome activation at the crux of severe COVID-19. Nat. Rev. Immunol. 21, 694–703 (2021).
pubmed: 34373622
pmcid: 8351223
doi: 10.1038/s41577-021-00588-x
Booty, L. M. & Bryant, C. E. Gasdermin D and beyond—gasdermin-mediated pyroptosis in bacterial infections. J. Mol. Biol. 434, 167409 (2022).
pubmed: 34929200
doi: 10.1016/j.jmb.2021.167409
Liu, X., Xia, S., Zhang, Z., Wu, H. & Lieberman, J. Channelling inflammation: gasdermins in physiology and disease. Nat. Rev. Drug Discov. 20, 384–405 (2021).
pubmed: 33692549
pmcid: 7944254
doi: 10.1038/s41573-021-00154-z
Broz, P., Pelegrín, P. & Shao, F. The gasdermins, a protein family executing cell death and inflammation. Nat. Rev. Immunol. 20, 143–157 (2020).
pubmed: 31690840
doi: 10.1038/s41577-019-0228-2
Kuang, S. et al. Structure insight of GSDMD reveals the basis of GSDMD auto-inhibition in cell pyroptosis. Proc. Natl Acad. Sci. USA 114, 10642–10647 (2017).
pubmed: 28928145
pmcid: 5635896
doi: 10.1073/pnas.1708194114
Kagan, J. C., Magupalli, V. G. & Wu, H. SMOCs: supramolecular organizing centres that control innate immunity. Nat. Rev. Immunol. 14, 821–826 (2014).
pubmed: 25359439
pmcid: 4373346
doi: 10.1038/nri3757
Schroder, K. & Tschopp, J. The inflammasomes. Cell 140, 821–832 (2010).
pubmed: 20303873
doi: 10.1016/j.cell.2010.01.040
Shi, J. et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514, 187–192 (2014).
pubmed: 25119034
doi: 10.1038/nature13683
Baker, P. J. et al. NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. Eur. J. Immunol. 45, 2918–2926 (2015).
pubmed: 26173988
doi: 10.1002/eji.201545655
Rühl, S. & Broz, P. Caspase-11 activates a canonical NLRP3 inflammasome by promoting K
pubmed: 26173909
doi: 10.1002/eji.201545772
Wang, K. et al. Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis. Cell 180, 941–955 (2020).
pubmed: 32109412
doi: 10.1016/j.cell.2020.02.002
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).
pubmed: 32553275
pmcid: 7382298
doi: 10.1016/j.immuni.2020.06.007
Yang, J. et al. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. Proc. Natl Acad. Sci. USA 115, 6792–6797 (2018).
pubmed: 29891674
pmcid: 6042100
doi: 10.1073/pnas.1800562115
Hu, Y. et al. The gasdermin D N-terminal fragment acts as a negative feedback system to inhibit inflammasome-mediated activation of caspase-1/11. Proc. Natl Acad. Sci. USA 119, e2210809119 (2022).
pubmed: 36322773
pmcid: 9659347
doi: 10.1073/pnas.2210809119
Bibo-Verdugo, B., Snipas, S. J., Kolt, S., Poreba, M. & Salvesen, G. S. Extended subsite profiling of the pyroptosis effector protein gasdermin D reveals a region recognized by inflammatory caspase-11. J. Biol. Chem. 295, 11292–11302 (2020).
Devant, P., Cao, A. & Kagan, J. C. Evolution-inspired redesign of the LPS receptor caspase-4 into an interleukin-1β–converting enzyme. Sci. Immunol. 6, eabh3567 (2021).
pubmed: 34734155
pmcid: 8559778
doi: 10.1126/sciimmunol.abh3567
Kambara, H. et al. Gasdermin D exerts anti-inflammatory effects by promoting neutrophil death. Cell Rep. 22, 2924–2936 (2018).
pubmed: 29539421
pmcid: 5878047
doi: 10.1016/j.celrep.2018.02.067
Burgener, S. S. et al. Cathepsin G inhibition by Serpinb1 and Serpinb6 prevents programmed necrosis in neutrophils and monocytes and reduces GSDMD-driven inflammation. Cell Rep. 27, 3646–3656 (2019).
pubmed: 31216481
pmcid: 7350907
doi: 10.1016/j.celrep.2019.05.065
Sollberger, G. et al. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps. Sci. Immunol. 3, eaar6689 (2018).
pubmed: 30143555
doi: 10.1126/sciimmunol.aar6689
Chen, K. W. et al. Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps. Sci. Immunol. 3, eaar6676 (2018).
pubmed: 30143554
doi: 10.1126/sciimmunol.aar6676
Stojkov, D. et al. NET formation is independent of gasdermin D and pyroptotic cell death. Sci. Signal. 16, eabm0517 (2023).
pubmed: 36693132
doi: 10.1126/scisignal.abm0517
Chauhan, D. et al. GSDMD drives canonical inflammasome‐induced neutrophil pyroptosis and is dispensable for NETosis. EMBO Rep. 23, e54277 (2022).
pubmed: 35899491
doi: 10.15252/embr.202154277
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).
pubmed: 30381458
pmcid: 6243247
doi: 10.1073/pnas.1809548115
Orning, P. et al. Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science 362, 1064–1069 (2018).
pubmed: 30361383
pmcid: 6522129
doi: 10.1126/science.aau2818
Palmer, L. E., Pancetti, A. R., Greenberg, S. & Bliska, J. B. YopJ of Yersinia spp. is sufficient to cause downregulation of multiple mitogen-activated protein kinases in eukaryotic cells. Infect. Immun. 67, 708–716 (1999).
pubmed: 9916081
pmcid: 96377
doi: 10.1128/IAI.67.2.708-716.1999
Rosadini, C. V. et al. A single bacterial immune evasion strategy dismantles both MyD88 and TRIF signaling pathways downstream of TLR4. Cell Host Microbe 18, 682–693 (2015).
pubmed: 26651944
pmcid: 4685476
doi: 10.1016/j.chom.2015.11.006
Demarco, B. et al. Caspase-8–dependent gasdermin D cleavage promotes antimicrobial defense but confers susceptibility to TNF-induced lethality. Sci. Adv. 6, eabc3465 (2020).
Mascarenhas, D. P. A. et al. Inhibition of caspase-1 or gasdermin-D enable caspase-8 activation in the Naip5/NLRC4/ASC inflammasome. PLoS Pathog. 13, e1006502 (2017).
pubmed: 28771586
pmcid: 5542441
doi: 10.1371/journal.ppat.1006502
Schneider, K. S. et al. The inflammasome drives GSDMD-independent secondary pyroptosis and IL-1 release in the absence of caspase-1 protease activity. Cell Rep. 21, 3846–3859 (2017).
pubmed: 29281832
pmcid: 5750195
doi: 10.1016/j.celrep.2017.12.018
Taabazuing, C. Y., Okondo, M. C. & Bachovchin, D. A. Pyroptosis and apoptosis pathways engage in bidirectional crosstalk in monocytes and macrophages. Cell Chem. Biol. 24, 507–514 (2017).
pubmed: 28392147
pmcid: 5467448
doi: 10.1016/j.chembiol.2017.03.009
Zhou, Z. et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science 368, eaaz7548 (2020).
pubmed: 32299851
doi: 10.1126/science.aaz7548
Wang, Y. et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547, 99–103 (2017).
pubmed: 28459430
doi: 10.1038/nature22393
Orzalli, M. H. et al. Virus-mediated inactivation of anti-apoptotic Bcl-2 family members promotes Gasdermin-E-dependent pyroptosis in barrier epithelial cells. Immunity 54, 1447–1462 (2021).
pubmed: 33979579
pmcid: 8594743
doi: 10.1016/j.immuni.2021.04.012
Zhang, J. et al. The metabolite α-KG induces GSDMC-dependent pyroptosis through death receptor 6-activated caspase-8. Cell Res. 31, 980–997 (2021).
pubmed: 34012073
pmcid: 8410789
doi: 10.1038/s41422-021-00506-9
Hou, J. et al. PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis. Nat. Cell Biol. 22, 1264–1275 (2020).
pubmed: 32929201
pmcid: 7653546
doi: 10.1038/s41556-020-0575-z
Deng, W. et al. Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis. Nature 602, 496–502 (2022).
pubmed: 35110732
pmcid: 9703647
doi: 10.1038/s41586-021-04384-4
LaRock, D. L. et al. Group A Streptococcus induces GSDMA-dependent pyroptosis in keratinocytes. Nature 605, 527–531 (2022).
pubmed: 35545676
pmcid: 9186297
doi: 10.1038/s41586-022-04717-x
Kao, Y. -T. et al. Zika virus cleaves GSDMD to disseminate prognosticable and controllable oncolysis in a human glioblastoma cell model. Mol. Ther. Oncolytics 28, 104–117 (2023).
pubmed: 36699618
pmcid: 9845690
doi: 10.1016/j.omto.2022.12.008
Remick, B. C., Gaidt, M. M. & Vance, R. E. Effector-triggered immunity. Annu. Rev. Immunol. 41, 453–481 (2023).
pubmed: 36750319
doi: 10.1146/annurev-immunol-101721-031732
Lei, X. et al. Enterovirus 71 Inhibits pyroptosis through cleavage of gasdermin D. J. Virol. 91, e01069–17 (2017).
pubmed: 28679757
pmcid: 5571240
doi: 10.1128/JVI.01069-17
Planès, R. et al. Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells. Mol. Cell 82, 2385–2400 (2022).
pubmed: 35594856
pmcid: 9108100
doi: 10.1016/j.molcel.2022.04.033
Liu, Z. et al. Crystal structures of the full-length murine and human gasdermin D reveal mechanisms of auto-inhibition, lipid binding, and oligomerization. Immunity 51, 43–49 (2019).
pubmed: 31097341
pmcid: 6640092
doi: 10.1016/j.immuni.2019.04.017
Xia, S. et al. Gasdermin D pore structure reveals preferential release of mature interleukin-1. Nature 593, 607–611 (2021).
pubmed: 33883744
pmcid: 8588876
doi: 10.1038/s41586-021-03478-3
Ruan, J., Xia, S., Liu, X., Lieberman, J. & Wu, H. Cryo-EM structure of the gasdermin A3 membrane pore. Nature 557, 62–67 (2018).
pubmed: 29695864
pmcid: 6007975
doi: 10.1038/s41586-018-0058-6
Wang, C. et al. Structural basis for GSDMB pore formation and its targeting by IpaH7.8. Nature 616, 590–597 (2023).
Zhong, X. et al. Structural mechanisms for regulation of GSDMB pore-forming activity. Nature 616, 598–605 (2023).
Schaefer, S. L. & Hummer, G. Sublytic gasdermin-D pores captured in atomistic molecular simulations. Elife 11, e81432 (2022).
pubmed: 36374182
pmcid: 9699695
doi: 10.7554/eLife.81432
Mari, S. A. et al. Gasdermin-A3 pore formation propagates along variable pathways. Nat. Commun. 13, 2609 (2022).
pubmed: 35545613
pmcid: 9095878
doi: 10.1038/s41467-022-30232-8
Mulvihill, E. et al. Mechanism of membrane pore formation by human gasdermin‐D. EMBO J. 37, e98321 (2018).
pubmed: 29898893
pmcid: 6043855
doi: 10.15252/embj.201798321
Santa Cruz Garcia, A. B., Schnur, K. P., Malik, A. B. & Mo, G. C. H. Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry. Nat. Commun. 13, 52 (2022).
pubmed: 35013201
pmcid: 8748731
doi: 10.1038/s41467-021-27692-9
Xie, W. J., Xia, S., Warshel, A. & Wu, H. Electrostatic influence on IL-1 transport through the GSDMD pore. Proc. Natl Acad. Sci. USA 119, e2120287119 (2022).
pubmed: 35115408
pmcid: 8833203
doi: 10.1073/pnas.2120287119
Russo, A. J. et al. Intracellular immune sensing promotes inflammation via gasdermin D–driven release of a lectin alarmin. Nat. Immunol. 22, 154–165 (2021).
pubmed: 33398185
pmcid: 8916041
doi: 10.1038/s41590-020-00844-7
de Vasconcelos, N. M., Van Opdenbosch, N., Van Gorp, H., Parthoens, E. & Lamkanfi, M. Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture. Cell Death Differ. 26, 146–161 (2019).
pubmed: 29666477
doi: 10.1038/s41418-018-0106-7
DiPeso, L., Ji, D. X., Vance, R. E. & Price, J. V. Cell death and cell lysis are separable events during pyroptosis. Cell Death Discov. 3, 17070 (2017).
pubmed: 29147575
pmcid: 5682879
doi: 10.1038/cddiscovery.2017.70
Bertheloot, D. et al. Nanobodies dismantle post‐pyroptotic ASC specks and counteract inflammation in vivo. EMBO Mol. Med. 14, e15415 (2022).
pubmed: 35438238
pmcid: 9174887
doi: 10.15252/emmm.202115415
Kayagaki, N. et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 591, 131–136 (2021).
pubmed: 33472215
doi: 10.1038/s41586-021-03218-7
Volchuk, A., Ye, A., Chi, L., Steinberg, B. E. & Goldenberg, N. M. Indirect regulation of HMGB1 release by gasdermin D. Nat. Commun. 11, 4561 (2020).
pubmed: 32917873
pmcid: 7486936
doi: 10.1038/s41467-020-18443-3
Tsuchiya, K. et al. Gasdermin D mediates the maturation and release of IL-1α downstream of inflammasomes. Cell Rep. 34, 108887 (2021).
pubmed: 33761363
doi: 10.1016/j.celrep.2021.108887
Chao, Y.-Y. et al. Human T
Yamagishi, R. et al. Gasdermin D–mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma. Sci. Immunol. 7, eabl7209 (2022).
pubmed: 35749514
doi: 10.1126/sciimmunol.abl7209
Chen, W. et al. Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion. Nat. Immunol. 23, 1021–1030 (2022).
pubmed: 35794369
doi: 10.1038/s41590-022-01255-6
Zhao, M. et al. Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and gasdermin C. Immunity 55, 623–638 (2022).
pubmed: 35385697
pmcid: 9109499
doi: 10.1016/j.immuni.2022.03.009
Zanoni, I. et al. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science 352, 1232–1236 (2016).
pubmed: 27103670
pmcid: 5111085
doi: 10.1126/science.aaf3036
Zanoni, I., Tan, Y., Di Gioia, M., Springstead, J. R. & Kagan, J. C. By capturing inflammatory lipids released from dying cells, the receptor CD14 induces inflammasome-dependent phagocyte hyperactivation. Immunity 47, 697–709 (2017).
pubmed: 29045901
pmcid: 5747599
doi: 10.1016/j.immuni.2017.09.010
Zhivaki, D. et al. Inflammasomes within hyperactive murine dendritic cells stimulate long-lived T cell-mediated anti-tumor immunity. Cell Rep. 33, 108381 (2020).
pubmed: 33207188
pmcid: 7727444
doi: 10.1016/j.celrep.2020.108381
Wolf, A. J. et al. Hexokinase is an innate immune receptor for the detection of bacterial peptidoglycan. Cell 166, 624–636 (2016).
pubmed: 27374331
pmcid: 5534359
doi: 10.1016/j.cell.2016.05.076
Hatscher, L. et al. Select hyperactivating NLRP3 ligands enhance the T
pubmed: 33906973
doi: 10.1126/scisignal.abe1757
Chen, K. W. et al. The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute salmonella challenge. Cell Rep. 8, 570–582 (2014).
pubmed: 25043180
doi: 10.1016/j.celrep.2014.06.028
Boucher, D. et al. Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. J. Exp. Med. 215, 827–840 (2018).
pubmed: 29432122
pmcid: 5839769
doi: 10.1084/jem.20172222
Gaidt, M. M. et al. Human monocytes engage an alternative inflammasome pathway. Immunity 44, 833–846 (2016).
pubmed: 27037191
doi: 10.1016/j.immuni.2016.01.012
Zhou, B. & Abbott, D. W. Gasdermin E permits interleukin-1 beta release in distinct sublytic and pyroptotic phases. Cell Rep. 35, 108998 (2021).
pubmed: 33852854
pmcid: 8106763
doi: 10.1016/j.celrep.2021.108998
Borges, J. P. et al. Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. Elife 11, e78609 (2022).
pubmed: 36468682
pmcid: 9754625
doi: 10.7554/eLife.78609
Araki, T. & Milbrandt, J. Ninjurin, a novel adhesion molecule, is induced by nerve injury and promotes axonal growth. Neuron 17, 353–361 (1996).
pubmed: 8780658
doi: 10.1016/S0896-6273(00)80166-X
Araki, T., Zimonjic, D. B., Popescu, N. C. & Milbrandt, J. Mechanism of homophilic binding mediated by ninjurin, a novel widely expressed adhesion molecule. J. Biol. Chem. 272, 21373–21380 (1997).
pubmed: 9261151
doi: 10.1074/jbc.272.34.21373
Odoardi, F. et al. T cells become licensed in the lung to enter the central nervous system. Nature 488, 675–679 (2012).
pubmed: 22914092
doi: 10.1038/nature11337
Bjanes, E. et al. Genetic targeting of Card19 is linked to disrupted NINJ1 expression, impaired cell lysis, and increased susceptibility to Yersinia infection. PLoS Pathog. 17, e1009967 (2021).
pubmed: 34648590
pmcid: 8547626
doi: 10.1371/journal.ppat.1009967
Wang, G., Zhang, D., Orchard, R. C., Hancks, D. C. & Reese, T. A. Norovirus MLKL-like protein initiates cell death to induce viral egress. Nature 616, 152–158 (2023).
Jorgensen, I., Zhang, Y., Krantz, B. A. & Miao, E. A. Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis. J. Exp. Med. 213, 2113–2128 (2016).
pubmed: 27573815
pmcid: 5030797
doi: 10.1084/jem.20151613
Fink, S. L. & Cookson, B. T. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell. Microbiol. 8, 1812–1825 (2006).
pubmed: 16824040
doi: 10.1111/j.1462-5822.2006.00751.x
Weinberg, J. M., Bienholz, A. & Venkatachalam, M. A. The role of glycine in regulated cell death. Cell. Mol. Life Sci. 73, 2285–2308 (2016).
pubmed: 27066896
pmcid: 4955867
doi: 10.1007/s00018-016-2201-6
Andrews, N. W. & Corrotte, M. Plasma membrane repair. Curr. Biol. 28, R392–R397 (2018).
pubmed: 29689221
doi: 10.1016/j.cub.2017.12.034
Cooper, S. T. & McNeil, P. L. Membrane repair: mechanisms and pathophysiology. Physiol. Rev. 95, 1205–1240 (2015).
pubmed: 26336031
pmcid: 4600952
doi: 10.1152/physrev.00037.2014
McCullough, J., Frost, A. & Sundquist, W. I. Structures, functions and dynamics of ESCRT-III/Vps4 membrane remodeling and fission complexes. Annu. Rev. Cell Dev. Biol. 34, 85–109 (2018).
pubmed: 30095293
pmcid: 6241870
doi: 10.1146/annurev-cellbio-100616-060600
Gong, Y.-N. et al. ESCRT-III acts downstream of MLKL to regulate necroptotic cell death and its consequences. Cell 169, 286–300 (2017).
pubmed: 28388412
pmcid: 5443414
doi: 10.1016/j.cell.2017.03.020
Rühl, S. et al. ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation. Science 362, 956–960 (2018).
pubmed: 30467171
doi: 10.1126/science.aar7607
Li, Z. et al. Enhancing gasdermin-induced tumor pyroptosis through preventing ESCRT-dependent cell membrane repair augments antitumor immune response. Nat. Commun. 13, 6321 (2022).
pubmed: 36280674
pmcid: 9592600
doi: 10.1038/s41467-022-34036-8
Nozaki, K. et al. Caspase-7 activates ASM to repair gasdermin and perforin pores. Nature 606, 960–967 (2022).
pubmed: 35705808
pmcid: 9247046
doi: 10.1038/s41586-022-04825-8
Tam, C. et al. Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. J. Cell Biol. 189, 1027–1038 (2010).
pubmed: 20530211
pmcid: 2886342
doi: 10.1083/jcb.201003053
Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847–856 (2008).
pubmed: 18604214
pmcid: 2834784
doi: 10.1038/ni.1631
Gaidt, M. M. et al. The DNA inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3. Cell 171, 1110–1124 (2017).
pubmed: 29033128
pmcid: 5901709
doi: 10.1016/j.cell.2017.09.039
Muñoz-Planillo, R. et al. K
pubmed: 23809161
pmcid: 3730833
doi: 10.1016/j.immuni.2013.05.016
Zheng, Z. et al. The lysosomal Rag–Ragulator complex licenses RIPK1– and caspase-8–mediated pyroptosis by Yersinia. Science 372, eabg0269 (2021).
pubmed: 35058659
pmcid: 8769499
doi: 10.1126/science.abg0269
Averette, K. M. et al. Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release Is Nlrp1b/Nalp1b-dependent. PLoS ONE 4, e7913 (2009).
pubmed: 19924255
pmcid: 2775945
doi: 10.1371/journal.pone.0007913
Karmakar, M. et al. N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis. Nat. Commun. 11, 2212 (2020).
pubmed: 32371889
pmcid: 7200749
doi: 10.1038/s41467-020-16043-9
Rogers, C. et al. Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation. Nat. Commun. 10, 1689 (2019).
pubmed: 30976076
pmcid: 6459836
doi: 10.1038/s41467-019-09397-2
Platnich, J. M. et al. Shiga toxin/lipopolysaccharide activates caspase-4 and Gasdermin D to trigger mitochondrial reactive oxygen species upstream of the NLRP3 inflammasome. Cell Rep. 25, 1525–1536 (2018).
pubmed: 30404007
doi: 10.1016/j.celrep.2018.09.071
Torre‐Minguela, C., Gómez, A. I., Couillin, I. & Pelegrín, P. Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis. FASEB J. 35, e21757 (2021).
pubmed: 34233045
doi: 10.1096/fj.202100085R
Huang, L. S. et al. mtDNA Activates cGAS signaling and suppresses the YAP-Mediated endothelial cell proliferation program to promote inflammatory injury. Immunity 52, 475–486 (2020).
pubmed: 32164878
pmcid: 7266657
doi: 10.1016/j.immuni.2020.02.002
Kondolf, H. C., D’Orlando, D. A., Dubyak, G. R. & Abbott, D. W. Protein engineering reveals that gasdermin A preferentially targets mitochondrial membranes over the plasma membrane during pyroptosis. J. Biol. Chem. 299, 102908 (2023).
pubmed: 36642180
pmcid: 9943860
doi: 10.1016/j.jbc.2023.102908
Zhang, F.-R. et al. Genomewide association study of leprosy. N. Engl. J. Med. 361, 2609–2618 (2009).
pubmed: 20018961
doi: 10.1056/NEJMoa0903753
Hui, K. Y. et al. Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease. Sci. Transl. Med. 10, eaai7795 (2018).
pubmed: 29321258
pmcid: 6028002
doi: 10.1126/scitranslmed.aai7795
Weindel, C. G. et al. Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis. Cell 185, 3214–3231 (2022).
pubmed: 35907404
doi: 10.1016/j.cell.2022.06.038
Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221–225 (2011).
pubmed: 21124315
doi: 10.1038/nature09663
Bauernfeind, F. et al. Cutting Edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 Inflammasome. J. Immunol. 187, 613–617 (2011).
pubmed: 21677136
doi: 10.4049/jimmunol.1100613
Semino, C., Carta, S., Gattorno, M., Sitia, R. & Rubartelli, A. Progressive waves of IL-1β release by primary human monocytes via sequential activation of vesicular and gasdermin D-mediated secretory pathways. Cell Death Dis. 9, 1088 (2018).
pubmed: 30352992
pmcid: 6199333
doi: 10.1038/s41419-018-1121-9
Wang, Y. et al. Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation. J. Mol. Cell. Biol. 11, 1069–1082 (2019).
pubmed: 30860577
pmcid: 6934151
doi: 10.1093/jmcb/mjz020
Bradfield, C. J. et al. Biphasic JNK signaling reveals distinct MAP3K complexes licensing inflammasome formation and pyroptosis. Cell Death Differ. 30, 589–604 (2023).
Evavold, C. L. et al. Control of gasdermin D oligomerization and pyroptosis by the Ragulator–Rag–mTORC1 pathway. Cell 184, 4495–4511 (2021).
pubmed: 34289345
pmcid: 8380731
doi: 10.1016/j.cell.2021.06.028
Devant, P. et al. Gasdermin D pore-forming activity is redox-sensitive. Cell Rep. 42, 112008 (2023).
pubmed: 36662620
pmcid: 9947919
doi: 10.1016/j.celrep.2023.112008
Balasubramanian, A. et al. Palmitoylation of gasdermin D directs its membrane translocation and pore formation in pyroptosis. Preprint at bioRxiv https://doi.org/10.1101/2023.02.21.529402 (2023).
Du, G. et al. ROS-dependent palmitoylation is an obligate licensing modification for GSDMD pore formation. Preprint at bioRxiv https://doi.org/10.1101/2023.03.07.531538 (2023).
Johnson, A. G. et al. Bacterial gasdermins reveal an ancient mechanism of cell death. Science 375, 221–225 (2022).
pubmed: 35025633
pmcid: 9134750
doi: 10.1126/science.abj8432
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).
pubmed: 32332857
pmcid: 7181755
doi: 10.1038/s41419-020-2476-2
Bambouskova, M. et al. Itaconate confers tolerance to late NLRP3 inflammasome activation. Cell Rep. 34, 108756 (2021).
pubmed: 33691097
pmcid: 8039864
doi: 10.1016/j.celrep.2021.108756
Hooftman, A. et al. The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation. Cell Metab. 32, 468–478 (2020).
pubmed: 32791101
pmcid: 7422798
doi: 10.1016/j.cmet.2020.07.016
Humphries, F. et al. Succination inactivates gasdermin D and blocks pyroptosis. Science 369, 1633–1637 (2020).
pubmed: 32820063
pmcid: 8744141
doi: 10.1126/science.abb9818
Hu, J. J. et al. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat. Immunol. 21, 736–745 (2020).
pubmed: 32367036
pmcid: 7316630
doi: 10.1038/s41590-020-0669-6
Rathkey, J. K. et al. Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci. Immunol. 3, eaat2738 (2018).
pubmed: 30143556
pmcid: 6462819
doi: 10.1126/sciimmunol.aat2738
Wang, C. et al. NLRP3 inflammasome activation triggers gasdermin D–independent inflammation. Sci. Immunol. 6, eabj3859 (2021).
pubmed: 34678046
pmcid: 8780201
doi: 10.1126/sciimmunol.abj3859
Li, Y., Pu, D., Huang, J., Zhang, Y. & Yin, H. Protein phosphatase 1 regulates phosphorylation of gasdermin D and pyroptosis. Chem. Commun. 58, 11965–11968 (2022).
doi: 10.1039/D2CC03590A
Hornbeck, P. V. et al. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 43, D512–D520 (2015).
pubmed: 25514926
doi: 10.1093/nar/gku1267
Shi, Y. et al. E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis. CellDeath Dis. 13, 106 (2022).
Luchetti, G. et al. Shigella ubiquitin ligase IpaH7.8 targets gasdermin D for degradation to prevent pyroptosis and enable infection. Cell Host Microbe 29, 1521–1530(2021).
pubmed: 34492225
pmcid: 9122893
doi: 10.1016/j.chom.2021.08.010
Hansen, J. M. et al. Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions. Cell 184, 3178–3191 (2021).
pubmed: 34022140
pmcid: 8221529
doi: 10.1016/j.cell.2021.04.036
Yin, H. et al. Insights into the GSDMB-mediated cellular lysis and its targeting by IpaH7.8. Nat. Commun. 14, 61 (2023).
pubmed: 36599845
pmcid: 9813358
doi: 10.1038/s41467-022-35725-0
Chai, Q. et al. A bacterial phospholipid phosphatase inhibits host pyroptosis by hijacking ubiquitin. Science 378, eabq0132 (2022).
pubmed: 36227980
doi: 10.1126/science.abq0132
Wein, T. & Sorek, R. Bacterial origins of human cell-autonomous innate immune mechanisms. Nat. Rev. Immunol. 22, 629–638 (2022).
pubmed: 35396464
doi: 10.1038/s41577-022-00705-4
Daskalov, A. & Glass, N. L. Gasdermin and gasdermin-like pore-forming proteins in invertebrates, fungi and bacteria. J. Mol. Biol. 434, 167273 (2022).
pubmed: 34599942
doi: 10.1016/j.jmb.2021.167273
Angosto-Bazarra, D. et al. Evolutionary analyses of the gasdermin family suggest conserved roles in infection response despite loss of pore-forming functionality. BMC Biol. 20, 9 (2022).
pubmed: 34996441
pmcid: 8742441
doi: 10.1186/s12915-021-01220-z
Jones, J. D. G., Vance, R. E. & Dangl, J. L. Intracellular innate immune surveillance devices in plants and animals. Science 354, aaf6395 (2016).
pubmed: 27934708
doi: 10.1126/science.aaf6395
Gao, L. A. et al. Prokaryotic innate immunity through pattern recognition of conserved viral proteins. Science 377, eabm4096 (2022).
pubmed: 35951700
pmcid: 10028730
doi: 10.1126/science.abm4096
De Schutter, E. et al. Punching holes in cellular membranes: biology and evolution of gasdermins. Trends Cell Biol. 31, 500–513 (2021).
pubmed: 33771452
doi: 10.1016/j.tcb.2021.03.004
Yuan, Z., Jiang, S., Qin, K. & Sun, L. New insights into the evolutionary dynamic and lineage divergence of gasdermin E in metazoa. Front. Cell Dev. Biol. 10, 952015 (2022).
pubmed: 35938154
pmcid: 9355259
doi: 10.3389/fcell.2022.952015
Jiang, S., Gu, H., Zhao, Y. & Sun, L. Teleost gasdermin E Is cleaved by caspase 1, 3 and 7 and induces pyroptosis. J. Immunol. 203, 1369–1382 (2019).
pubmed: 31391231
doi: 10.4049/jimmunol.1900383
Xu, H., Jiang, S., Yu, C., Yuan, Z. & Sun, L. GSDMEa-mediated pyroptosis is bi-directionally regulated by caspase and required for effective bacterial clearance in teleost. Cell Death Dis. 13, 491 (2022).
pubmed: 35610210
pmcid: 9130220
doi: 10.1038/s41419-022-04896-5
Li, H. et al. Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis. Front. Immunol. 13, 078526 (2023).
doi: 10.3389/fimmu.2022.1078526
Jiang, S., Zhou, Z., Sun, Y., Zhang, T. & Sun, L. Coral gasdermin triggers pyroptosis. Sci. Immunol. 5, eabd2591 (2020).
pubmed: 33277371
doi: 10.1126/sciimmunol.abd2591
Daskalov, A., Gladieux, P., Heller, J. & Glass, N. L. Programmed cell death in neurospora crassa is controlled by the allorecognition determinant rcd-1. Genetics 213, 1387–1400 (2019).
pubmed: 31636083
pmcid: 6893366
doi: 10.1534/genetics.119.302617
Daskalov, A., Mitchell, P. S., Sandstrom, A., Vance, R. E. & Glass, N. L. Molecular characterization of a fungal gasdermin-like protein. Proc. Natl Acad. Sci. USA 117, 18600–18607 (2020).
pubmed: 32703806
pmcid: 7414189
doi: 10.1073/pnas.2004876117
Clavé, C. et al. Fungal gasdermin-like proteins are controlled by proteolytic cleavage. Proc. Natl Acad. Sci. USA 119, 2109418119 (2022).
doi: 10.1073/pnas.2109418119