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They can be activated simultaneously within tissues or cell lines and are often associated with various diseases. Thus, identifying a common player and inhibitor targeting several PCD types is essential. Here, we show that overexpression and oligomerization of the mitochondrial gatekeeper voltage-dependent anion channel 1 (VDAC1) is involved in apoptosis, pyroptosis, and ferroptosis, and specific VDAC1 oligomerization inhibitors, VBIT-4 and VBIT-12, prevented multiple forms of PCD triggered by various stimuli. In addition, they mitigated mitochondrial dysfunction, reduced reactive oxygen species production and intracellular Ca\n                    <jats:sup>2<\/jats:sup>\n                    \u207a levels, preserved mitochondrial-associated hexokinase, and inhibited assembly\/activation of the NLRP3 inflammasome. In Alzheimer\u2019s disease and inflammatory bowel disease mouse models, VBIT-4 and VBIT-12, respectively, protected against apoptosis, pyroptosis, ferroptosis, and disease-associated pathologies. Thus, we show that VDAC1 oligomerization represents a prime target for VBIT-4 and VBIT-12 that can simultaneously inhibit various PCD forms and diseases associated with enhanced PCD and\/or inflammation.\n                  <\/jats:p>","DOI":"10.1007\/s10495-025-02217-7","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:35:20Z","timestamp":1775910920000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting VDAC1 to protect against mitochondria-linked cell death pathways: apoptosis, pyroptosis, ferroptosis, and associated diseases"],"prefix":"10.1007","volume":"31","author":[{"given":"A.","family":"Shteinfer-Kuzmine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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