{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:18:00Z","timestamp":1772162280493,"version":"3.50.1"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"35","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,9,2]]},"abstract":"<jats:p>\n                    Nucleic acid and histone modifications critically depend on the tricarboxylic acid (TCA) cycle for substrates and cofactors. Although a few TCA cycle enzymes have been reported in the nucleus, the corresponding pathways are considered to operate in mitochondria. Here, we show that a part of the TCA cycle is operational also in the nucleus. Using\n                    <jats:sup>13<\/jats:sup>\n                    C-tracer analysis, we identified activity of glutamine-to-fumarate, citrate-to-succinate, and glutamine-to-aspartate routes in the nuclei of\n                    <jats:italic>HeLa<\/jats:italic>\n                    cells. Proximity labeling mass spectrometry revealed a spatial vicinity of the involved enzymes with core nuclear proteins. We further show nuclear localization of aconitase 2 and 2-oxoglutarate dehydrogenase in mouse embryonic stem cells. Nuclear localization of the latter enzyme, which produces succinyl-CoA, changed from pluripotency to a differentiated state with accompanying changes in the nuclear protein succinylation. Together, our results demonstrate operation of an extended metabolic pathway in the nucleus, warranting a revision of the canonical view on metabolic compartmentalization.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abq5206","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T13:57:41Z","timestamp":1661954261000},"source":"Crossref","is-referenced-by-count":67,"title":["Operation of a TCA cycle subnetwork in the mammalian nucleus"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9550-4487","authenticated-orcid":true,"given":"Eleni","family":"Kafkia","sequence":"first","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Heidelberg, Germany."},{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5801-4024","authenticated-orcid":true,"given":"Amparo","family":"Andres-Pons","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Heidelberg, Germany."},{"name":"Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2641-9024","authenticated-orcid":true,"given":"Kerstin","family":"Ganter","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Rome, Italy."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9600-6620","authenticated-orcid":true,"given":"Markus","family":"Seiler","sequence":"additional","affiliation":[{"name":"Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0697-8777","authenticated-orcid":true,"given":"Tom S.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, UK."}]},{"given":"Anna","family":"Andrejeva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, UK."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1075-7448","authenticated-orcid":true,"given":"Paula","family":"Jouhten","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Heidelberg, Germany."},{"name":"VTT Technical Research Center of Finland, Helsinki, Finland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0557-8480","authenticated-orcid":true,"given":"Filipa","family":"Pereira","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Heidelberg, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2288-1518","authenticated-orcid":true,"given":"Catarina","family":"Franco","sequence":"additional","affiliation":[{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]},{"given":"Anna","family":"Kuroshchenkova","sequence":"additional","affiliation":[{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-5366","authenticated-orcid":true,"given":"Sergio","family":"Leone","sequence":"additional","affiliation":[{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]},{"given":"Ritwick","family":"Sawarkar","sequence":"additional","affiliation":[{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-3391","authenticated-orcid":true,"given":"Rebecca","family":"Boston","sequence":"additional","affiliation":[{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-074X","authenticated-orcid":true,"given":"James","family":"Thaventhiran","sequence":"additional","affiliation":[{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-4040","authenticated-orcid":true,"given":"Judith B.","family":"Zaugg","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Heidelberg, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0594-6543","authenticated-orcid":true,"given":"Kathryn S.","family":"Lilley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Cambridge, UK."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-7374","authenticated-orcid":true,"given":"Christophe","family":"Lancrin","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Rome, Italy."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-1321","authenticated-orcid":true,"given":"Martin","family":"Beck","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Heidelberg, Germany."},{"name":"Max Planck Institute of Biophysics, Frankfurt, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6166-8640","authenticated-orcid":true,"given":"Kiran Raosaheb","family":"Patil","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory (EMBL), Heidelberg, Germany."},{"name":"The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK."}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.05.004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.191056.112"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-8-89"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19353"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13981"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.07.002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.43"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.12.014"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R114.046664"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2762"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3796"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24294"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1577-5"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3209"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.06.008"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2363-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-0270-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf4382"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.046"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.2741\/4572"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-017-0026-3"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25003"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000328"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.026"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.08.014"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709747104"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)30124-2"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.71"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164097"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2013-0271"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00965850"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-017-0077-z"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1930"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12040"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not015"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(62)90061-7"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.042499"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E15-12-0844"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.084"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2017.10.010"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0037-y"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.07.024"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa029"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-019-02780-x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116085"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08191-w"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0032-0"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.12.015"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-417160-2.00006-0"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2006.08.001"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv514"},{"key":"e_1_3_3_54_2","first-page":"D296","article-title":"ELM-The eukaryotic linear motif resource in 2020","volume":"48","author":"Kumar M.","year":"2020","unstructured":"M. Kumar, M. Gouw, S. Michael, H. S\u00e1mano-S\u00e1nchez, R. Pancsa, J. Glavina, A. Diakogianni, J. A. Valverde, D. Bukirova, J. Signaly\u0161eva, N. Palopoli, N. E. Davey, L. B. Chemes, T. J. Gibson, ELM-The eukaryotic linear motif resource in 2020. Nucleic Acids Res. 48, D296\u2013D306 (2020).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-144"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201112098"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20177608"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200904048"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.16.00562"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2018.03.006"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.101"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.suppl_1.S96"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr645"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2557"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22112"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw199"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1049"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4330"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29312"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.0c00313"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu013"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-2-r14"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.014050"},{"key":"e_1_3_3_78_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini Y.","year":"1995","unstructured":"Y. Benjamini, Y. Hochberg, Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B Stat. Methodol. 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. Series B Stat. Methodol."},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1106"},{"key":"e_1_3_3_80_2","first-page":"D440","article-title":"MetaboLights: A resource evolving in response to the needs of its scientific community","volume":"48","author":"Haug K.","year":"2020","unstructured":"K. Haug, K. Cochrane, V. C. Nainala, M. Williams, J. Chang, K. V. Jayaseelan, C. O\u2019Donovan, MetaboLights: A resource evolving in response to the needs of its scientific community. Nucleic Acids Res. 48, D440\u2013D444 (2020).","journal-title":"Nucleic Acids Res."}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.abq5206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T20:40:11Z","timestamp":1727901611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abq5206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":79,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2022,9,2]]}},"alternative-id":["10.1126\/sciadv.abq5206"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.abq5206","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.11.22.393413","asserted-by":"object"}]},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]},"article-number":"eabq5206"}}