TY  - JOUR
A1  - Kafkia, Eleni
A1  - Andres-Pons, Amparo
A1  - Ganter, Kerstin
A1  - Seiler, Markus
A1  - Smith, Tom S.
A1  - Andrejeva, Anna
A1  - Jouhten, Paula
A1  - Pereira, Filipa
A1  - Franco, Catarina
A1  - Kuroshchenkova, Anna
A1  - Leone, Sergio
A1  - Sawarkar, Ritwick
A1  - Boston, Rebecca
A1  - Thaventhiran, James
A1  - Zaugg, Judith B.
A1  - Lilley, Kathryn S.
A1  - Lancrin, Christophe
A1  - Beck, Martin
A1  - Patil, Kiran Raosaheb
T1  - Operation of a TCA cycle subnetwork in the mammalian nucleus
T2  - Science advances
N2  - 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 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. 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.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74800
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-748007
SN  - 2375-2548
VL  - 8
IS  - 35, art. eabq5206
PB  - American Association for the Advancement of Science
CY  - Washington, DC [u.a.]
ER  -