PXD022608

PXD022608 is an original dataset announced via ProteomeXchange.

Title	Operation of a TCA cycle subnetwork in the mammalian nucleus
Description	Nucleic acid and histone modifications critically depend on central metabolism for substrates and co-factors. Although a few enzymes related to the formation of these metabolites have been reported in the nucleus, the corresponding metabolic pathways are considered to function elsewhere in the cell. Here we show that a substantial part of the mitochondrial tricarboxylic acid (TCA) cycle, the biosynthetic hub of epigenetic modification factors, is operational also in the nucleus. Using 13C-tracer analysis, we identified activity of glutamine-to-fumarate, citrate-to-succinate, and glutamine-to-aspartate routes in the nuclei of HeLa cells. Proximity labeling mass-spectrometry revealed a spatial vicinity of the involved enzymes with core nuclear proteins, supporting their nuclear location. We further show nuclear localization of aconitase 2 and 2-oxoglutarate dehydrogenase in mouse embryonic stem cells. Together, our results demonstrate operation of an extended metabolic pathway in the nucleus warranting a revision of the canonical view on metabolic compartmentalization and gene expression regulation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:17:31.775.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-18 08:16:32	ID requested
1	2022-10-13 14:30:07	announced
⏵ 2	2023-11-14 07:17:32	announced	2023-11-14: Updated project metadata.

Kafkia E, Andres-Pons A, Ganter K, Seiler M, Smith TS, Andrejeva A, Jouhten P, Pereira F, Franco C, Kuroshchenkova A, Leone S, Sawarkar R, Boston R, Thaventhiran J, Zaugg JB, Lilley KS, Lancrin C, Beck M, Patil KR, Operation of a TCA cycle subnetwork in the mammalian nucleus. Sci Adv, 8(35):eabq5206(2022) [pubmed]

submitter keyword: Nucleus, Metabolic Pathways, Proximity-biotinylation Mass Spectrometry, Stable Isotope Metabolomics Study

Kiran Raosaheb Patil
contact affiliation	MRC Toxicology Unit, University of Cambridge
contact email	kp533@mrc-cam.ac.uk
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/10/PXD022608

PRIDE project URI

• PRIDE
  1. PXD022608
     1. Label: PRIDE project
     2. Name: Operation of a TCA cycle subnetwork in the mammalian nucleus