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Disulfiram blocks mitochondrial permeabilization and reduces PANoptotic signaling by preventing GSDMD-NT, GSDME-NT and p-MLKL binding to mitochondria, limiting reactive oxygen species, release of components, and PANoptosome assembly. In an HLH mouse model, disulfiram decreases systemic inflammation and mitigates liver, lung, and kidney injury.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/anti-alcoholism-drug-disulram-inhibits-panoptosis-by-blocking-mitochondrial-permeabilization-in-macrophages/415536/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/anti-alcoholism-drug-disulram-inhibits-panoptosis-by-blocking-mitochondrial-permeabilization-in-macrophages/415536.png","ImageObject",300,407,{"name":42,"@type":43},"Aria Callaghan","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is PANoptosis and why is it relevant here?","Question",{"text":63,"@type":64},"PANoptosis is an inflammatory cell death modality that simultaneously activates pyroptosis, apoptosis, and necroptosis signaling. This work evaluates whether disulfiram can interfere with PANoptosis-related inflammatory disease processes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does disulfiram affect mitochondrial events during PANoptosis?",{"text":68,"@type":64},"Disulfiram prevents mitochondrial permeabilization by blocking the binding of GSDMD-NT, GSDME-NT, and p-MLKL to mitochondria, which reduces mitochondrial dysfunction, release of PANoptotic components, and reactive oxygen species generation.",{"name":70,"@type":61,"acceptedAnswer":71},"What therapeutic benefit does disulfiram show in the HLH mouse model?",{"text":72,"@type":64},"In vivo, intraperitoneal disulfiram substantially decreases systemic inflammation and mitigates liver, lung, and kidney injury. These effects coincide with reduced activation of PANoptosis signaling in those organs.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},415536,1790742677,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},962084926284,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","TYPE Original Research PUBLISHED 19 December 2025 DOI 10.3389/fimmu.2025.1726408  \nOPEN ACCESS  \nEDITED BY  \nDaming Zuo,  \nSouthern Medical University, China  \nREVIEWED BY  \nYungeng Wei,  \nFirst Affiliated Hospital of Guangzhou Medical University, China  \nJie Xu,  \nIowa State University, United States  \n*CORRESPONDENCE  \nDong-yun Ouyang  \n [dongyun1967@aliyun.com](dongyun1967@aliyun.com)[ ](dongyun1967@aliyun.com)Xian-hui He  \n [thexh@jnu.edu.cn](thexh@jnu.edu.cn)[ ](thexh@jnu.edu.cn)Qing-bing Zha  \n [zhaqingbb@sina.com](zhaqingbb@sina.com)  \n†These authors have contributed equally to this work  \nRECEIVED 16 October 2025  \nREVISED 05 December 2025  \nACCEPTED 08 December 2025  \nPUBLISHED 19 December 2025  \nCORRECTED 16 January 2026  \nCITATION  \nLi Y-p, Niu X-j, Zhang G, Chan O-k, Sun N, Hu B, Shi Z-j, Ouyang D-y, He X-h and Zha Q-b (2025) Anti-alcoholism drug disulfiram inhibits PANoptosis by blocking mitochondrial permeabilizationin macrophages.  \nFront. Immunol. 16:1726408 .  \ndoi: 10.3389/fimmu.2025.1726408  \nCOPYRIGHT  \n© 2025 Li, Niu, Zhang, Chan, Sun, Hu, Shi, Ouyang, He and Zha. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) .  \nThe use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nAnti-alcoholism drug disulfiram inhibits PANoptosis by blocking mitochondrial permeabilizationin macrophages  \nYa-ping Li 1,2†, Xin-jian Niu 2†, Ge Zhang 3†, On-kei Chan 2, Nuo Sun 2, Bo Hu 3, Zi-jian Shi 4, Dong-yun Ouyang 1,2*, Xian-hui He 2,4* and Qing-bing Zha 1,5*  \n1 Department of Clinical Laboratory, the Sixth Affiliated Hospital of Jinan University (Dongguan Eastern Central Hospital), Dongguan, China, 2 Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University, Guangzhou, China, 3 Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou, China, 4 Department of Fetal Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, China, 5Center of Reproductive Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, China  \nIntroduction: PANoptosis is a form of inflammatory cell death that exhibits simultaneous activation of pyroptosis, apoptosis and necroptosis signaling. Disulfiram is a clinically used anti-alcoholism drug and can inhibit NLRP3 inflammasome activation and pyroptosis. However, it is unknown whether and how disulfiram interferes with PANoptosis and related inflammatory diseases. Methods: PANoptosis was induced in murine macrophages and related protein levels were assayed by immunoblotting. The effects of disulfiram on PANoptosis were assessed both in macrophages in vitro and in a mouse model of hemophagocytic lymphohistiocytosis (HLH) in vivo.  \nResults: Mitochondrial permeabilization preceded lytic cell death upon PANoptosis and binding of GSDMD-NT, GSDME-NT and p-MLKL to mitochondria was linked to mitochondrial dysfunction, which was depending on cardiolipin synthesis in mitochondria. Intriguingly, disulfiram not only prevented mitochondrial permeabilization but also suppressed PANoptotic signaling activation in macrophages. Mechanistically, disulfiram prevented the binding of GSDMD-NT, GSDME-NT and p-MLKL from mitochondria to attenuate its permeabilization, release of its components and generation of reactive oxygen species. Furthermore, the assembly of PANoptosome was effectively blocked by disulfiram. In a mouse model of HLH, intraperitoneal administration of disulfiram substantially decreased systemic inflammation and mitigated liver, lung and kidney injury, which were accompanied by reduced activation of PANoptosis signaling in these organs.  \nConclusion: A previously unappreciated action of d","cbCaiv1mZKKvTPzA","https://ap.wps.com/l/cbCaiv1mZKKvTPzA","pdf",39898789,23,"English","# Introduction\n## Inflammatory cell death and PANoptosis\n# Methods\n## Macrophage induction and protein assays\n## In vivo HLH model\n# Results\n## Mitochondrial permeabilization and PANoptotic signaling\n## Disulfiram mechanism and PANoptosome assembly\n## Protective effects in HLH organs\n# Conclusion","[{\"question\":\"What is PANoptosis and why is it relevant here?\",\"answer\":\"PANoptosis is an inflammatory cell death modality that simultaneously activates pyroptosis, apoptosis, and necroptosis signaling. This work evaluates whether disulfiram can interfere with PANoptosis-related inflammatory disease processes.\"},{\"question\":\"How does disulfiram affect mitochondrial events during PANoptosis?\",\"answer\":\"Disulfiram prevents mitochondrial permeabilization by blocking the binding of GSDMD-NT, GSDME-NT, and p-MLKL to mitochondria, which reduces mitochondrial dysfunction, release of PANoptotic components, and reactive oxygen species generation.\"},{\"question\":\"What therapeutic benefit does disulfiram show in the HLH mouse model?\",\"answer\":\"In vivo, intraperitoneal disulfiram substantially decreases systemic inflammation and mitigates liver, lung, and kidney injury. These effects coincide with reduced activation of PANoptosis signaling in those organs.\"}]","Anti-alcoholism drug disulfiram inhibits PANoptosis by blocking mitochondrial permeabilization in macrophages | PDF",1790601808,58]