PXD078273

PXD078273 is an original dataset announced via ProteomeXchange.

Title	Acetyl-CoA dependent processes are preferentially supported by local metabolite synthesis - Labeling experiment
Description	The cell nucleus is an active site of metabolism. Multiple metabolic enzymes that classically function in cytosolic or mitochondrial pathways have been documented within cell nuclei, where they participate in gene regulation, DNA replication, and DNA repair. However, 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, yet the biological significance of its nuclear-cytosolic distribution is incompletely understood. Here, we leveraged cell lines in which ACLY is localized 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 compartment-localized ACLY enables fine-tuning of both processes. Nuclear ACLY preserves histone H3K23 acetylation under glucose limitation and modulates specific transcriptional programs, including suppression of fatty acid and cholesterol synthesis genes. Conversely, cytosolic ACLY most efficiently supports fatty acid synthesis, elongation, and membrane lipid biosynthetic fluxes, reflecting local substrate production and high FASN expression. The data indicate that metabolites such as acetyl-CoA can diffuse between the nucleus and cytosol, but that local synthesis defines a preferential metabolic fate for products, enabling more precise control of cellular processes.
HostingRepository	PRIDE
AnnounceDate	2026-08-26
AnnouncementXML	Submission_2026-08-26_11:09:34.108.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-13 07:22:18	ID requested
⏵ 1	2026-08-26 11:09:34	announced

Dataset with its publication pending

submitter keyword: ACLY localization shapes acetyl-CoA use

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. PXD078273
     1. Label: PRIDE project
     2. Name: Acetyl-CoA dependent processes are preferentially supported by local metabolite synthesis - Labeling experiment