{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:52:13Z","timestamp":1792785133830,"version":"4.5.0"},"reference-count":33,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DHAC | National Health and Medical Research Council","award":["2025759"],"award-info":[{"award-number":["2025759"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Plasma membrane rupture (PMR) is a terminal event in many forms of lytic cell death, yet was long regarded as a passive consequence of osmotic swelling and mechanical membrane failure. The identification of ninjurin-1 (NINJ1) as a key mediator of PMR fundamentally changed this view by establishing that membrane permeabilisation and terminal membrane rupture are mechanistically distinct processes. Across different cell death modalities, NINJ1 promotes the transition from membrane damage to catastrophic cellular disintegration. Structural studies have revealed how NINJ1 is restrained by autoinhibition in healthy cells and assembles into higher-order membrane-remodelling complexes following activation. However, how NINJ1 is activated and how its assemblies cooperate with the physical state of the dying cell to produce membrane rupture remain incompletely understood. NINJ1-dependent PMR also determines the release of intracellular contents, linking cell death to inflammation, host defence, tissue homeostasis and disease. Emerging evidence suggests that NINJ1 integrates molecular, metabolic and biophysical signals and can function beyond canonical cell-death pathways. Here, we discuss the molecular mechanisms governing NINJ1-mediated PMR, how diverse cell death pathways converge on this process, and how terminal membrane rupture shapes inflammatory responses, host defence and tissue pathology. We further consider unresolved mechanisms of NINJ1 activation and the therapeutic potential of uncoupling cell death from inflammatory membrane rupture.<\/jats:p>","DOI":"10.1042\/bst20260842","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:54:10Z","timestamp":1791874450000},"page":"1487-1495","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NINJ1-mediated membrane rupture bridges cell death to tissue inflammation"],"prefix":"10.1042","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6305-5870","authenticated-orcid":false,"given":"Thu\u00a0Uyen","family":"Tran","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Chemistry, Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5588-9957","authenticated-orcid":false,"given":"Quan\u00a0Thinh","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6524-8206","authenticated-orcid":false,"given":"Tuong-Khanh\u00a0My","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5802-1603","authenticated-orcid":false,"given":"Thanh\u00a0Kha","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"2026101302540519800_B1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1158\/2159-8290.CD-20-0789","article-title":"Modes of regulated cell death in cancer","volume":"11","author":"Koren","year":"2021","journal-title":"Cancer Discov."},{"key":"2026101302540519800_B2","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: recommendations of the 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