Dataset Information

Operation of a TCA cycle subnetwork in the mammalian nucleus

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Frank Stein

LAB HEAD: Kiran Raosaheb Patil

PROVIDER: PXD022608 | Pride | 2022-10-13

REPOSITORIES: Pride

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			Action	DRS
	Ernie_181214_P0808_MR_EK_IP_TMT10_rep1_fr1.raw	Raw
	Ernie_181214_P0808_MR_EK_IP_TMT10_rep1_fr2.raw	Raw
	Ernie_181214_P0808_MR_EK_IP_TMT10_rep1_fr3.raw	Raw
	Ernie_181214_P0808_MR_EK_IP_TMT10_rep1_fr4.raw	Raw
	Ernie_181214_P0808_MR_EK_IP_TMT10_rep1_fr5.raw	Raw

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Operation of a TCA cycle subnetwork in the mammalian nucleus.

Kafkia Eleni E Andres-Pons Amparo A Ganter Kerstin K Seiler Markus M Smith Tom S TS Andrejeva Anna A Jouhten Paula P Pereira Filipa F Franco Catarina C Kuroshchenkova Anna A Leone Sergio S Sawarkar Ritwick R Boston Rebecca R Thaventhiran James J Zaugg Judith B JB Lilley Kathryn S KS Lancrin Christophe C Beck Martin M Patil Kiran Raosaheb KR

Science advances 20220831 35

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 <sup>13</sup>C-tracer analysis, we identified activity of glutamine-to-fumarate, citrate-to-succinate, and glutamine-to-aspartate routes in the nuclei o ...[more]

PMID: 36044572

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