Golgi-derived vesicles containing PI(3,4)P 2 drive mitochondrial fusion
Mitochondria are dynamic organelles that remodel their shape to regulate cell fate. Mitochondrial division involves interactions with the endoplasmic reticulum (ER), lysosomes, and trans-Golgi network–derived 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 2 ] 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 α and β (PI3K-C2α and PI3K-C2β), which generate PI(3,4)P 2 , led to mitochondrial fragmentation resulting from impaired fusion. Furthermore, cardiomyocyte-specific PI3K-C2α and PI3K-C2β double-deletion mice exhibited mitochondrial fragmentation and heart failure. Thus, subpopulations of Golgi-derived vesicles carrying different phosphoinositides control mitochondrial membrane remodeling and homeostasis.
Authors
- Vincent Anton (ORCID: https://orcid.org/0000-0003-3008-6346)
- Maki Sugaya
- Tsuyoshi Osawa (ORCID: https://orcid.org/0000-0002-9479-6665)
- Ikuko Koyama‐Honda (ORCID: https://orcid.org/0000-0001-9321-9682)
- Kazuaki Yoshioka (ORCID: https://orcid.org/0000-0002-8631-3846)
- Ayumu Sugiura (ORCID: https://orcid.org/0000-0002-4776-1478)
- Ikuroh Ohsawa (ORCID: https://orcid.org/0000-0002-7212-9298)
- Shigeru Yanagi (ORCID: https://orcid.org/0000-0002-1392-8663)
- Mayuko Segawa (ORCID: https://orcid.org/0000-0002-5680-9576)
- Dane M. Wolf (ORCID: https://orcid.org/0000-0002-0811-1114)
- Masahiro Morita (ORCID: https://orcid.org/0000-0002-8627-084X)
- Yasunori Fujita (ORCID: https://orcid.org/0009-0006-0334-7212)
- Yusuke Hirabayashi (ORCID: https://orcid.org/0000-0003-3950-6781)
- Koki Nakamura (ORCID: https://orcid.org/0000-0003-4885-4526)
- Julien Prudent (ORCID: https://orcid.org/0000-0003-3821-6088)
- Sakie Katsumura (ORCID: https://orcid.org/0000-0001-9271-1448)
- Shun Nagashima (ORCID: https://orcid.org/0000-0001-8042-0897)
- Sho Aki (ORCID: https://orcid.org/0000-0002-5787-2075)
- Isshin Shiiba (ORCID: https://orcid.org/0000-0002-8093-1782)
- Mark A. Johnson (ORCID: https://orcid.org/0009-0000-1772-2702)
- Hisamichi Naito (ORCID: https://orcid.org/0000-0002-0750-1743)
- Yoh Takuwa
- Suvagata Roy Chowdhury
- Joe Ganellin (ORCID: https://orcid.org/0009-0003-8633-7674)
Institutions
- Kanazawa University (JP)
- Tokyo University of Pharmacy and Life Sciences (JP)
- Kanazawa Medical University (JP)
- The University of Texas at San Antonio Health Science Center (US)
- Tohoku University (JP)
- University of Cambridge (GB)
- Juntendo University (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Gakushuin University (JP)
- The University of Tokyo (JP)
- MRC Mitochondrial Biology Unit (GB)
- The University of Osaka (JP)
Publication Details
- Journal
- Science
- Published
- 2026-10-08
- DOI
- https://doi.org/10.1126/science.adx9628
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00