PXD070188-1

PXD070188 is an original dataset announced via ProteomeXchange.

Title	Acetyl-CoA dependent processes are preferentially supported by local metabolite synthesis
Description	The cell nucleus has emerged as an active site of metabolism. Multiple metabolic enzymes that classically function in cytosolic or mitochondrial pathways have also been documented within nuclei where they impact gene expression and cell phenotypes. Yet, metabolites can passively diffuse across nuclear pores, and the extent to which the nucleus and cytosol are continuous versus distinct metabolic compartments remains unclear. Both the nucleus and cytosol require acetyl-CoA for specific processes (e.g., histone acetylation and lipid synthesis, respectively), and the acetyl-CoA producing enzyme ATP-citrate lyase (ACLY) is present in both locations. However, the mechanisms governing ACLY’s nuclear localization and the biological significance of its nuclear-cytosolic distribution are incompletely understood. Here, we leveraged cell lines in which ACLY is restricted to either the nucleus or cytosol to investigate its compartmentalized functions. We find that ACLY in either location can support both fatty acid synthesis and histone acetylation, but that compartment-localized ACLY enables fine-tuning of both processes. Nuclear ACLY preserves histone H3K23 acetylation under glucose limitation and regulates specific transcriptional programs including fatty acid and cholesterol synthesis genes, which are suppressed by either WT or nuclear ACLY. Conversely, cytosolic ACLY most efficiently supports fatty acid synthesis and elongation, reflecting both local substrate production and high lipogenesis enzyme levels. The data indicate that acetyl-CoA can diffuse between the nucleus and cytosol, but that local metabolite synthesis enables finer control of cellular processes, suggesting a framework for understanding nuclear metabolism.
HostingRepository	PRIDE
AnnounceDate	2026-08-26
AnnouncementXML	Submission_2026-08-26_11:24:22.122.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monomethylated residue; acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-01 15:18:13	ID requested
⏵ 1	2026-08-26 11:24:22	announced

Dataset with its publication pending

submitter keyword: metabolism,ACLY, metabolic compartmentalization, lipid regulation

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070188
     1. Label: PRIDE project
     2. Name: Acetyl-CoA dependent processes are preferentially supported by local metabolite synthesis