Cell ResearchPub Date : 2025-04-03DOI: 10.1038/s41422-025-01107-6
Petr Broz
{"title":"Pyroptosis: molecular mechanisms and roles in disease","authors":"Petr Broz","doi":"10.1038/s41422-025-01107-6","DOIUrl":"10.1038/s41422-025-01107-6","url":null,"abstract":"Pyroptosis is a type of programmed necrosis triggered by the detection of pathogens or endogenous danger signals in the cytosol. Pyroptotic cells exhibit a swollen, enlarged morphology and ultimately undergo lysis, releasing their cytosolic contents — such as proteins, metabolites, and nucleic acids — into the extracellular space. These molecules can function as danger-associated molecular patterns (DAMPs), triggering inflammation when detected by neighboring cells. Mechanistically, pyroptosis is initiated by members of the gasdermin protein family, which were identified a decade ago as pore-forming executors of cell death. Mammalian gasdermins consist of a cytotoxic N-terminal domain, a flexible linker, and a C-terminal regulatory domain that binds to and inhibits the N-terminus. Proteolytic cleavage within the linker releases the N-terminal domain, enabling it to target various cellular membranes, including nuclear, mitochondrial, and plasma membranes, where it forms large transmembrane pores. Gasdermin pores in the plasma membrane disrupt the electrochemical gradient, leading to water influx and cell swelling. Their formation also activates the membrane protein ninjurin-1 (NINJ1), which oligomerizes to drive complete plasma membrane rupture and the release of large DAMPs. Since their discovery as pore-forming proteins, gasdermins have been linked to pyroptosis not only in host defense but also in various pathological conditions. This review explores the history of pyroptosis, recent insights into gasdermin activation, the cellular consequences of pore formation, and the physiological roles of pyroptosis.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 5","pages":"334-344"},"PeriodicalIF":25.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-04-03DOI: 10.1038/s41422-025-01103-w
Deepshikha Malik, Ashish Deshmukh, Silvija Bilokapic, Mario Halic
{"title":"Mechanisms of chromatin remodeling by the human Snf2-type ATPase SNF2H","authors":"Deepshikha Malik, Ashish Deshmukh, Silvija Bilokapic, Mario Halic","doi":"10.1038/s41422-025-01103-w","DOIUrl":"10.1038/s41422-025-01103-w","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 6","pages":"465-468"},"PeriodicalIF":25.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Signal-induced NLRP3 phase separation initiates inflammasome activation","authors":"Gonglu Zou, Yuluan Tang, Jie Yang, Shuo Fu, Yuheng Li, Xuanyao Ren, Nanhai Zhou, Wenlong Zhao, Juyi Gao, Ziran Ruan, Zhengfan Jiang","doi":"10.1038/s41422-025-01096-6","DOIUrl":"10.1038/s41422-025-01096-6","url":null,"abstract":"NLRP3 inflammasome is activated by diverse stimuli including infections, intracellular and environmental irritants. How NLRP3 senses these unrelated stimuli and what activates NLRP3 remain unknown. Here we report that signal-dependent NLRP3 phase separation initiated its activation, in which the palmitoyltransferase ZDHHC7-mediated tonic NLRP3 palmitoylation and an IDR region in the FISNA domain of NLRP3 play important roles. Moreover, three conserved hydrophobic residues in the IDR critically mediate multivalent weak interactions. NLRP3-activating stimuli including K+ efflux and NLRP3-interacting molecules imiquimod, palmitate, and cardiolipin all cause NLRP3 conformational change and induce its phase separation and activation in cells and/or in vitro. Surprisingly, amphiphilic molecules like di-alcohols used to inhibit biomolecular phase separation and chemotherapeutic drugs doxorubicin and paclitaxel activate NLRP3 independently of ZDHHC7 by directly inducing NLRP3 phase separation. Mechanistically, amphiphilic molecules decrease the solubility of both palmitoylated and non-palmitoylated NLRP3 to directly induce its phase separation and activation while NLRP3 palmitoylation reduces its solubility to some extent without activation. Therefore, ZDHHC7-mediated NLRP3 palmitoylation in resting cells licenses its activation by lowering the threshold for NLRP3 phase separation in response to any of the diverse stimuli whereas NLRP3 solubility-reducing molecules like di-alcohols and chemotherapeutic drugs activate NLRP3 directly. The signal-induced NLRP3 phase separation likely provides the simplest and most direct mechanistic basis for NLRP3 activation.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 6","pages":"437-452"},"PeriodicalIF":25.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01096-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-03-25DOI: 10.1038/s41422-025-01101-y
Liujia Qian, Zhen Dong, Tiannan Guo
{"title":"Grow AI virtual cells: three data pillars and closed-loop learning","authors":"Liujia Qian, Zhen Dong, Tiannan Guo","doi":"10.1038/s41422-025-01101-y","DOIUrl":"10.1038/s41422-025-01101-y","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 5","pages":"319-321"},"PeriodicalIF":25.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-03-25DOI: 10.1038/s41422-025-01105-8
Panyu Fei, Michael L. Dustin
{"title":"Mechano-pharmacology of T cell receptor specificity","authors":"Panyu Fei, Michael L. Dustin","doi":"10.1038/s41422-025-01105-8","DOIUrl":"10.1038/s41422-025-01105-8","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 5","pages":"324-325"},"PeriodicalIF":25.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-03-25DOI: 10.1038/s41422-025-01102-x
Biyun Zhu, Shao Wei Hu, Yilai Shu
{"title":"Identification of a GPCR as a tip link-independent equilibrioceptor","authors":"Biyun Zhu, Shao Wei Hu, Yilai Shu","doi":"10.1038/s41422-025-01102-x","DOIUrl":"10.1038/s41422-025-01102-x","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 5","pages":"326-327"},"PeriodicalIF":25.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell ResearchPub Date : 2025-03-25DOI: 10.1038/s41422-025-01106-7
Benjamin A. Plog, Leon C. D. Smyth, Jonathan Kipnis
{"title":"The night shift: norepinephrine drives glymphatics","authors":"Benjamin A. Plog, Leon C. D. Smyth, Jonathan Kipnis","doi":"10.1038/s41422-025-01106-7","DOIUrl":"10.1038/s41422-025-01106-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 9","pages":"621-622"},"PeriodicalIF":25.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}