Academic Journal
Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol.
| Τίτλος: | Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol. |
|---|---|
| Συγγραφείς: | Zhou X; Stem Cells and Metabolism Research Program and Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Minerva Foundation Institute for Medical Research, Helsinki, Finland., van der Stoel MM; Stem Cells and Metabolism Research Program and Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Minerva Foundation Institute for Medical Research, Helsinki, Finland., Kaptan S; Department of Physics, University of Helsinki, Helsinki, Finland., Li H; Stem Cells and Metabolism Research Program and Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Minerva Foundation Institute for Medical Research, Helsinki, Finland., Li S; Stem Cells and Metabolism Research Program and Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Minerva Foundation Institute for Medical Research, Helsinki, Finland., Hölttä M; Stem Cells and Metabolism Research Program and Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Minerva Foundation Institute for Medical Research, Helsinki, Finland., Vihinen H; Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Jokitalo E; Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Thiele C; Life and Medical Science Institute, University of Bonn, Bonn, Germany., Pietiläinen O; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Morioka S; Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Sasaki J; Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Sasaki T; Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Vattulainen I; Department of Physics, University of Helsinki, Helsinki, Finland., Ikonen E; Stem Cells and Metabolism Research Program and Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland. elina.ikonen@helsinki.fi.; Minerva Foundation Institute for Medical Research, Helsinki, Finland. elina.ikonen@helsinki.fi. |
| Πηγή: | Nature communications [Nat Commun] 2025 Aug 21; Vol. 16 (1), pp. 7808. Date of Electronic Publication: 2025 Aug 21. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| Ιατρικοί όροι (MeSH): | Cholesterol*/metabolism , Golgi Apparatus*/metabolism , Phosphatidylinositol Phosphates*/metabolism , Vacuolar Proton-Translocating ATPases*/metabolism , Vacuolar Proton-Translocating ATPases*/genetics , Phosphoric Monoester Hydrolases*/metabolism , Phosphoric Monoester Hydrolases*/genetics, trans-Golgi Network/metabolism ; Trophoblasts/metabolism ; Indoleacetic Acids/pharmacology ; Humans ; HeLa Cells ; HEK293 Cells ; Glycosylation ; Membrane Proteins |
| Περίληψη: | Sac1 is a conserved phosphoinositide phosphatase, whose loss-of-function compromises cell and organism viability. Here, we employ acute auxin-inducible Sac1 degradation to identify its immediate downstream effectors in human cells. Most of Sac1 is degraded in ~1 h, paralleled by increased PI(4)P and decreased cholesterol in the trans-Golgi network (TGN) during the following hour, and superseded by Golgi fragmentation, impaired glycosylation, and selective degradation of TGN proteins by ~4 h. The TGN disintegration results from its acute deacidification caused by disassembly of the Golgi V-ATPase. Mechanistically, Sac1 mediated TGN membrane composition maintains an assembly-promoting conformation of the V (© 2025. The Author(s).) |
| Competing Interests: | Competing interests: The authors declare no competing interests. |
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| Grant Information: | 332096 United Kingdom WT_ Wellcome Trust; 364185 Academy of Finland (Suomen Akatemia) |
| Substance Nomenclature: | 97C5T2UQ7J (Cholesterol) 0 (Phosphatidylinositol Phosphates) 0 (phosphatidylinositol 4-phosphate) EC 3.6.1.- (Vacuolar Proton-Translocating ATPases) 0 (Sac1 protein, mammalian) EC 3.1.3.2 (Phosphoric Monoester Hydrolases) 0 (Indoleacetic Acids) 0 (Membrane Proteins) |
| Entry Date(s): | Date Created: 20250821 Date Completed: 20250821 Latest Revision: 20260728 |
| Update Code: | 20260728 |
| PubMed Central ID: | PMC12371084 |
| DOI: | 10.1038/s41467-025-63125-7 |
| PMID: | 40841558 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2041-1723 |
|---|---|
| DOI: | 10.1038/s41467-025-63125-7 |