ArticleSignal transduction and targeted therapy2021
The existence of a nonclassical TCA cycle in the nucleus that wires the metabolic-epigenetic circuitry.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 89 citations in OpenAlex.
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- Nuclear-specific reductive carboxylation of alpha-ketoglutarate fuels histone acetylation to induce chromatin accessibility and gene activation.Nature communications · 2026Article
- Mechanism of Elevated COFoods (Basel, Switzerland) · 2026Article
- Lysosomes contribute to the synthesis of tricarboxylic acid-related metabolites in the hippocampus.Life metabolism · 2026Article
- Metabolic characterization of the tumor microenvironment orchestrates therapeutic strategies and clinical outcomes in pancreatic cancer.Nature communications · 2026Article
- Acetylated mitochondrial MDH2 regulates CTR2 transcription to induce cuproptosis during Escherichia coli infection.Nature communications · 2026Article
- OGDHL Promotes Prostate Cancer Progression and Regulates Neuroendocrine Marker Expression and Nucleotide Abundance.Molecular cancer research : MCR · 2026Article
- SPEND-hSRS imaging of fumarate uncovers mitochondrial metabolic heterogeneity.bioRxiv : the preprint server for biology · 2026Article
- Attenuated lamin A-prohibitin2 interaction leads to mitochondrial dysfunction in LMNA 289 A>G-mediated dilated cardiomyopathy.The Journal of biological chemistry · 2026Article
- Citric Acid Cycle Genes and Nutrigenetics.International journal of molecular sciences · 2026Review
- Redox-Guided Epigenetic Signaling in Cancer: miRNA-DNMT Feedback Loops as Epigenetic Memory Modulates.Antioxidants (Basel, Switzerland) · 2026Review
- Anaerobic self-induced fermentation: a green bioprocessing strategy for enhancing extraction efficiency and bioactivities of flavonoids from Erigeron breviscapus (Vant.) Hand-Mazz.Archives of microbiology · 2026Article
- Review
- Biallelic variants in IBA57 with multiple mitochondrial dysfunction syndrome 3.Frontiers in genetics · 2026Article
- The plant epigenome governed by nutrients and metabolism.Current opinion in plant biology · 2025Review
- Pharmacological induction of acetyl-CoA carboxylase 1 autophagic degradation attenuates lipid accumulation and cholangiocarcinoma progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Mitochondrial Dynamics in Aging Heart.Biomedicines · 2025Review
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- OGDHL regulates tumor growth, neuroendocrine marker expression, and nucleotide abundance in prostate cancer.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
23 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.
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