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Mitochondrial division involves interactions with the endoplasmic reticulum (ER), lysosomes, and trans-Golgi network\u2013derived vesicles to facilitate membrane scission. How interorganelle contacts regulate mitochondrial membrane fusion remains largely unknown. Here, we identified a role for Golgi-derived vesicles enriched in phosphatidylinositol 3,4-bisphosphate [PI(3,4)P\n                    <jats:sub>2<\/jats:sub>\n                    ] in regulating mitochondrial fusion. We found that these vesicles were recruited to ER- and mitofusin-marked fusion sites. Accordingly, loss of class II PI3-kinase isoforms \u03b1 and \u03b2 (PI3K-C2\u03b1 and PI3K-C2\u03b2), which generate PI(3,4)P\n                    <jats:sub>2<\/jats:sub>\n                    , led to mitochondrial fragmentation resulting from impaired fusion. Furthermore, cardiomyocyte-specific PI3K-C2\u03b1 and PI3K-C2\u03b2 double-deletion mice exhibited mitochondrial fragmentation and heart failure. Thus, subpopulations of Golgi-derived vesicles carrying different phosphoinositides control mitochondrial membrane remodeling and homeostasis.\n                  <\/jats:p>","DOI":"10.1126\/science.adx9628","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:00:31Z","timestamp":1791482431000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Golgi-derived vesicles containing PI(3,4)P\n                    <sub>2<\/sub>\n                    drive mitochondrial fusion"],"prefix":"10.1126","volume":"394","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5787-2075","authenticated-orcid":true,"given":"Sho","family":"Aki","sequence":"first","affiliation":[{"name":"Division of Nutriomics and Oncology, RCAST, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, Japan."},{"name":"Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 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