{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhou X"],"funding":["Academy of Finland (Suomen Akatemia)"],"pagination":["7808"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371084"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["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by increased PI(4)P and decreased cholesterol in the trans-Golgi network (TGN) during the following hour, and superseded by Golgi fragmentation, impaired glycosylation, and selective degradation of TGN proteins by ~4 h. The TGN disintegration results from its acute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 V0a2 subunit. Key phenotypes of acute Sac1 degradation are recapitulated in human differ"],"journal":["Nature communications"],"pubmed_title":["Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol."],"pmcid":["PMC12371084"],"funding_grant_id":["364185","332096"],"pubmed_authors":["Vihinen H","Sasaki J","Li H","Holtta M","Morioka S","Sasaki T","Zhou X","Li S","Thiele C","Jokitalo E","Ikonen E","Kaptan S","van der Stoel MM","Pietilainen O","Vattulainen I"],"additional_accession":[]},"is_claimable":false,"name":"Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol.","description":"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by increased PI(4)P and decreased cholesterol in the trans-Golgi network (TGN) during the following hour, and superseded by Golgi fragmentation, impaired glycosylation, and selective degradation of TGN proteins by ~4 h. The TGN disintegration results from its acute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 V0a2 subunit. Key phenotypes of acute Sac1 degradation are recapitulated in human differ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-08T06:53:01.251Z","creation":"2026-04-07T23:31:16.675Z"},"accession":"S-EPMC12371084","cross_references":{"pubmed":["40841558"],"doi":["10.1038/s41467-025-63125-7"]}}