PXD032238 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Operation of a TCA cycle subnetwork in the mammalian nucleus_mass4tox |
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 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-10-14 |
AnnouncementXML | Submission_2022-10-14_15:23:59.334.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD032238 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | CatarinaFranco |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-03-11 11:10:32 | ID requested | |
⏵ 1 | 2022-10-14 15:24:00 | announced | |
2 | 2023-11-14 08:01:33 | announced | 2023-11-14: Updated project metadata. |
Publication List
10.6019/PXD032238; |
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: tricarboxylic acid (TCA) cycle, nuclear proteins, non canonical metabolism compartmentalization, gene expression regulation |
Contact List
Kiran RaosahebPatil |
contact affiliation | MRC Toxicology Unit University of Cambridge |
contact email | kp533@cam.ac.uk |
lab head | |
CatarinaFranco |
contact affiliation | MRC Toxicology Unit University of Cambridge |
contact email | cd735@cam.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD032238
- Label: PRIDE project
- Name: Operation of a TCA cycle subnetwork in the mammalian nucleus_mass4tox