Cited by 6Cellular transport and secretionATP Synthase and ATPases ResearchLipid metabolism and biosynthesis

Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol

Open access
Zhou, Xin, van der Stoel, Miesje M., Kaptan, Shreyas, Li, Haoran, Li, Shiqian, Hölttä, Maarit, Vihinen, Helena, Jokitalo, Eija +7 more·2025·Nature Communications

Published version of a preprint

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by increased PI(4)P and decreased cholesterol in the trans- Golgi network (TGN) during the following hour, and superseded by Golgi fragmentation, impaired glycosylation, and selective degradation of TGN proteins by ~4 h. The TGN disintegration results from its acute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 V 0 a2 subunit. Key phenotypes of acute Sac1 degradation are recapitulated in human differentiated trophoblasts, causing processing defects of chorionic gonadotropin, in line with loss-of-function intolerance of the human SACM1L gene. Collectively, our findings reveal that the assembly of the Golgi V-ATPase is controlled by the TGN membrane via Sac1 fuelled lipid exchange.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-025-63125-7

Cites

108 of 108 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 109 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Zhou, X., van der Stoel, M. M., Kaptan, S., Li, H., Li, S., Hölttä, M., Vihinen, H., Jokitalo, E., Thiele, C., Pietiläinen, O., Morioka, S., Sasaki, J., Sasaki, T., Vattulainen, I., & Ikonen, E.
Affiliations
  • University of Helsinki (FI)
  • University of Bonn (DE)
  • Tokyo Medical and Dental University (JP)
Corresponding author
Ikonen, Elina
Venue
Nature Communications
Published
2025-08-21
Volume
16
Issue
1
Pages
7808-7808
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4413376468
Cited by
6
References
109
Citations by year
2026: 5 · 2025: 1
FWCI
2.98
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Academy of Finland (332096, 364185)
  • Jane ja Aatos Erkon Säätiö
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
Sac1, phosphoinositide phosphatase, trans-Golgi network, cholesterol, Golgi fragmentation, membrane acidification, lipid exchange, trophoblast, auxin-inducible degradation
MeSH terms
Cholesterol, Glycosylation, Golgi Apparatus, HeLa Cells, Humans, Indoleacetic Acids, Membrane Proteins, Phosphoric Monoester Hydrolases, Trophoblasts, Phosphatidylinositol Phosphates, trans-Golgi Network, Vacuolar Proton-Translocating ATPases, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review