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PXD032918

PXD032918 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOperation of a TCA cycle subnetwork in the mammalian nucleus
DescriptionNucleic acid and histone modifications critically depend on central metabolism for substrates and co-factors. Although a few enzymes related to the formation of these required 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. This dataset includes the data relating to the use of LOPIT to determine the subcellular localisation of succinylated proteins.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_07:57:34.447.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKathryn Lilley
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListN6-succinyl-L-lysine; deaminated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-04-02 12:05:17ID requested
12022-10-14 05:21:33announced
22023-11-14 07:57:38announced2023-11-14: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: succinylation, subcellular localisation,LOPIT, spatial proteomics
Contact List
Kiran Patil
contact affiliationMRC Toxicology Unit Gleeson Building Tennis Court Road Cambridge CB2 1QR
contact emailkp533@mrc-tox.cam.ac.uk
lab head
Kathryn Lilley
contact affiliationUniversity of Cambridge
contact emailksl23@cam.ac.uk
dataset submitter
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Dataset FTP location
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