Affinage

SLC25A1

Tricarboxylate transport protein, mitochondrial · UniProt P53007

Round 2 corrected
Length
311 aa
Mass
34.0 kDa
Annotated
2026-04-28
130 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC25A1 is an inner mitochondrial membrane antiporter that exports citrate (and isocitrate) from the mitochondrial matrix in exchange for cytosolic malate, thereby serving as the principal conduit for mitochondrial citrate to reach the cytoplasm where ATP citrate lyase (ACLY) converts it to acetyl-CoA (PMID:8514800, PMID:23266187). This citrate-to-acetyl-CoA axis supplies substrate for de novo lipogenesis, histone and protein acetylation critical for chromatin integrity and genome stability, and inflammatory mediator synthesis (NO, prostaglandins) downstream of NF-κB/STAT1 signaling in activated macrophages (PMID:19654186, PMID:21787310, PMID:25072865). SLC25A1-derived acetyl-CoA also sustains FSP1 acetylation to protect cells from ferroptosis, maintains redox homeostasis in cancer stem cells, and is regulated by IRAKM-dependent phosphorylation during IL-1β-driven lipogenesis in adipocytes and by KRAS–GLI1 transcriptional activation in pancreatic cancer (PMID:39881208, PMID:29651165, PMID:35585086, PMID:37695315). Recessive loss-of-function mutations in SLC25A1 cause combined D,L-2-hydroxyglutaric aciduria, a neurometabolic disorder characterized by impaired mitochondrial citrate efflux, 2-hydroxyglutarate accumulation, and neuromuscular dysfunction (PMID:23561848, PMID:26870663).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1993 High

    Cloning the rat liver tricarboxylate carrier established SLC25A1 as a mitochondrial carrier family member with a tripartite six-transmembrane-helix topology, providing the molecular identity needed for all subsequent functional studies.

    Evidence cDNA cloning from direct protein sequencing of purified rat liver carrier; hydrophobicity analysis

    PMID:8514800

    Open questions at the time
    • Human orthologue transport kinetics not yet characterized at this stage
    • No disease association established
  2. 2009 High

    Establishing that SLC25A1-mediated citrate export supplies cytosolic acetyl-CoA for histone acetylation answered why a metabolite transporter is essential for genome stability, linking mitochondrial metabolism to chromatin maintenance.

    Evidence Drosophila sea mutant genetics plus siRNA in human fibroblasts; chromosome breakage assays and global histone acetylation measurements

    PMID:19654186

    Open questions at the time
    • Specific histone marks affected not resolved
    • Whether acetyl-CoA depletion or citrate accumulation is the primary driver of breakage was not distinguished
  3. 2011 High

    Demonstrating that SLC25A1 is induced by LPS and required for NO, ROS, and prostaglandin production in macrophages established mitochondrial citrate export as a metabolic bottleneck in innate immune activation.

    Evidence siRNA knockdown and pharmacological CIC inhibition in LPS-stimulated macrophages; NO/ROS/prostaglandin quantification

    PMID:21787310

    Open questions at the time
    • Direct metabolic flux measurements of citrate export in immune cells not performed
    • Relative contribution of citrate versus other mitochondrial metabolites not fully dissected
  4. 2012 High

    Reconstitution of purified SLC25A1 in liposomes confirmed its identity as a citrate/malate antiporter, providing the biochemical gold standard for its transport mechanism.

    Evidence Heterologous expression, reconstitution into liposomes, direct transport assays

    PMID:23266187

    Open questions at the time
    • High-resolution structural basis of substrate selectivity not yet available
    • Regulatory post-translational modifications on the carrier not explored
  5. 2013 High

    Identification of recessive SLC25A1 mutations as the cause of combined D,L-2-hydroxyglutaric aciduria in 12 individuals answered the genetic basis of this neurometabolic disease and confirmed the physiological essentiality of mitochondrial citrate export.

    Evidence Whole-exome sequencing of affected families; stable isotope labeling in patient fibroblasts showing impaired citrate efflux

    PMID:23561848

    Open questions at the time
    • Precise mechanism linking citrate retention to 2-HG accumulation not fully delineated
    • Genotype–phenotype correlations across different mutations remain incomplete
  6. 2014 High

    Mapping transcriptional induction of SLC25A1 by TNFα/IFNγ via NF-κB and STAT1 placed the carrier within the inflammatory signaling cascade and identified IRAKM-mediated phosphorylation of SLC25A1 as a direct post-translational activating mechanism during IL-1β signaling in adipocytes.

    Evidence Cytokine stimulation with transcription factor inhibition; Co-IP of IRAKM with SLC25A1, kinase assays, adipocyte-specific knockout mice

    PMID:25072865 PMID:35585086

    Open questions at the time
    • Specific phosphorylation sites on SLC25A1 and their individual functional consequences not fully mapped
    • Whether phosphorylation alters transport kinetics or carrier stability not distinguished
  7. 2014 Medium

    Demonstrating NMJ defects in a patient with a homozygous SLC25A1 missense mutation and recapitulation in zebrafish knockdown expanded the disease phenotype beyond metabolic aciduria to include neuromuscular dysfunction.

    Evidence Patient exome sequencing, in vitro carrier function assay, zebrafish morpholino knockdown with NMJ morphology analysis

    PMID:26870663

    Open questions at the time
    • Whether NMJ defect is a direct consequence of local citrate depletion or secondary to systemic metabolic imbalance is unclear
    • Single-family study
  8. 2018 High

    Showing that SLC25A1 is upregulated in cancer stem cells and required for their redox balance, DNA repair, and self-renewal established SLC25A1 as a therapeutic vulnerability, with pharmacological inhibition being synthetic lethal with cisplatin or EGFR blockade.

    Evidence BTA and CNASB inhibitors in lung CSC sphere assays, ROS measurement, clonogenic survival, xenograft models

    PMID:29651165 PMID:29888201

    Open questions at the time
    • Specificity of BTA/CNASB for SLC25A1 versus other mitochondrial carriers not fully established
    • Patient-derived tumor responses not tested
  9. 2020 High

    Pharmacological and liver-specific genetic ablation of SLC25A1 in NAFLD/NASH mouse models reversed steatosis, obesity, and hyperglycemia by blunting PPARγ-driven lipogenesis and gluconeogenesis, demonstrating tissue-level metabolic functions.

    Evidence CTPI-2 treatment, global heterozygous and liver-conditional Slc25a1 knockout mice on high-fat diet; lipid profiling, glucose tolerance tests

    PMID:31959914

    Open questions at the time
    • Long-term safety of SLC25A1 inhibition in liver not assessed
    • Compensatory metabolic pathways upon chronic inhibition not characterized
  10. 2022 High

    Neuronal overexpression of SLC25A1 produced autistic-like behaviors, white matter disruption, and altered synaptic plasticity in mice, with acetyl-proteomics revealing region-specific protein acetylation changes, directly demonstrating that excess mitochondrial citrate export reprograms the neuronal acetylome.

    Evidence Forebrain-specific SLC25A1 transgenic mice; behavioral testing, MRI, electrophysiology, quantitative acetyl-proteomics

    PMID:35203088

    Open questions at the time
    • Causal link between specific acetylation targets and behavioral phenotype not established
    • Reversibility of phenotype upon SLC25A1 normalization not tested
  11. 2023 High

    Identification of the KRAS–GLI1–SLC25A1 transcriptional axis in pancreatic cancer revealed how oncogenic signaling co-opts mitochondrial citrate export to fuel lipogenesis and tumorigenesis, and showed that GLI1 directly binds the SLC25A1 promoter.

    Evidence ChIP for GLI1 at SLC25A1 promoter, KrasG12D mouse models, pharmacological SLC25A1/GLI1 inhibition, high-fat diet tumor studies

    PMID:37695315

    Open questions at the time
    • Whether GLI1-dependent regulation occurs in non-pancreatic KRAS-driven cancers not tested
    • Relative contribution of SLC25A1 versus other lipogenic enzymes to KRAS-driven tumor growth not quantified
  12. 2023 High

    Delineation of the SLC25A1→ACLY→acetyl-CoA→KAT2B→FSP1-K168-acetylation pathway established a direct mechanism by which mitochondrial citrate export protects cells from ferroptosis by preventing ubiquitin-dependent FSP1 degradation.

    Evidence CRISPR screen of SLC superfamily, CTPI-2 and ACLY inhibitors, FSP1 K168 mutagenesis, KAT2B/HDAC3 identification, in vivo ferroptosis assays

    PMID:39881208

    Open questions at the time
    • Whether this ferroptosis-protective mechanism operates in non-cancer cell types is unknown
    • Structural basis for KAT2B specificity toward FSP1-K168 not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of human SLC25A1 in distinct conformational states, the full catalog of regulatory phosphorylation sites and their kinases, and the in vivo therapeutic index of SLC25A1 inhibition in cancer and metabolic disease remain to be established.
  • No atomic-resolution structure of human SLC25A1 reported
  • Complete post-translational modification map (phosphorylation, acetylation) and their transport-kinetic consequences lacking
  • Clinical translatability of SLC25A1 inhibitors not assessed in human trials

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0005739 mitochondrion 5
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-382551 Transport of small molecules 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ACLYFSP1GLI1HDAC3IRAKMKAT2B

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The rat liver mitochondrial tricarboxylate transport protein (SLC25A1 ortholog) was cloned and its primary structure determined. The protein is 298 amino acids (mature form) with a 13-residue presequence, contains three related ~100-amino-acid sequence domains each with two predicted transmembrane α-helices (six total), placing it in the mitochondrial carrier family with a characteristic tripartite topology. cDNA cloning via PCR with primers from direct protein sequencing; hydrophobicity analysis; Southern blot The Journal of biological chemistry High 8514800
2009 Mutations in the Drosophila ortholog of SLC25A1 (scheggia/sea) impair citrate transport from mitochondria to cytosol, causing extensive chromosome breakage in mitotic cells, ATR-dependent cell cycle arrest, and a dramatic reduction in global histone acetylation. Loss of SLC25A1 by siRNA in human primary fibroblasts similarly leads to chromosome breaks and histone acetylation defects, establishing an evolutionarily conserved role for SLC25A1 in supplying cytosolic citrate (and downstream acetyl-CoA) for chromatin acetylation and genome stability. Drosophila genetics (sea mutants), siRNA knockdown in human fibroblasts, chromosome breakage assays, ATR pathway analysis, global histone acetylation measurement Human molecular genetics High 19654186
2011 The mitochondrial citrate carrier (CIC/SLC25A1) is induced at the mRNA and protein level by lipopolysaccharide in immune cells. Gene silencing or pharmacological inhibition of CIC significantly reduces production of nitric oxide, reactive oxygen species, and prostaglandins in activated macrophages, demonstrating that CIC-mediated citrate export is required for the generation of inflammatory mediators. LPS stimulation, CIC gene silencing (siRNA), CIC activity inhibition, NO/ROS/prostaglandin assays The Biochemical journal High 21787310
2012 SLC25A1 is a member of the mitochondrial carrier superfamily (SLC25) characterized by a tripartite structure, six transmembrane α-helices, and 3-fold repeated signature motifs embedded in the inner mitochondrial membrane. It functions as an antiporter exchanging citrate (and isocitrate) efflux from the mitochondrial matrix for cytosolic malate import. Comparative sequence analysis, heterologous expression, reconstitution into liposomes, transport assays Molecular aspects of medicine High 23266187
2013 Recessive loss-of-function mutations in SLC25A1 cause combined D-2- and L-2-hydroxyglutaric aciduria. Stable isotope labeling experiments in patient fibroblasts demonstrated impaired mitochondrial citrate efflux, and absence of SLC25A1 protein was shown in fibroblasts with certain mutations, establishing that SLC25A1 deficiency is the pathogenic mechanism underlying this neurometabolic disease. Whole exome sequencing, stable isotope labeling experiments in patient fibroblasts, immunoblotting for SLC25A1 protein American journal of human genetics High 23561848
2014 SLC25A1 is transcriptionally induced by TNFα and IFNγ via NF-κB and STAT1 transcription factors. The citrate exported from mitochondria via SLC25A1, and its downstream metabolic intermediate acetyl-CoA, are necessary for cytokine-induced nitric oxide and prostaglandin production, placing SLC25A1-mediated citrate export as a central node in the inflammatory metabolic pathway. Cytokine stimulation, transcription factor inhibition (NF-κB, STAT1), SLC25A1 knockdown, metabolite measurements (citrate, acetyl-CoA, NO, prostaglandins) Biochimica et biophysica acta High 25072865
2014 A homozygous missense mutation in SLC25A1 causes impaired neuromuscular junction (NMJ) function in addition to metabolic disease. Mutant SLC25A1 protein showed abnormal carrier function in vitro. Knockdown of SLC25A1 in zebrafish recapitulated the human disease phenotype with clear NMJ abnormalities and axonal outgrowth defects, suggesting the NMJ impairment is related to pre-synaptic nerve terminal defects secondary to mitochondrial citrate transport dysfunction. Whole exome sequencing, in vitro mutant carrier function assay, zebrafish SLC25A1 knockdown, NMJ morphology analysis Journal of neuromuscular diseases Medium 26870663
2014 SLC25A1 deficiency (combined D,L-2-hydroxyglutaric aciduria) leads to depletion of cytosolic citrate and accumulation of intramitochondrial citrate. Citrate supplementation (but not malate) in a patient reduced urinary D2HG and L2HG levels and stabilized seizure frequency, consistent with the model that impaired SLC25A1-mediated citrate export drives accumulation of 2-hydroxyglutarate species. Clinical metabolite monitoring (organic acid profiling), citrate vs. malate treatment intervention in a patient Journal of inherited metabolic disease Medium 24687295
2016 Severe neonatal SLC25A1 deficiency (homozygous p.Arg198His, within the putative substrate-binding site I of the carrier) results in lactic acidosis, reduced mitochondrial spare respiratory capacity, and increased glycolytic flux in patient fibroblasts, demonstrating that loss of mitochondrial citrate export impairs mitochondrial bioenergetics and forces metabolic reprogramming toward glycolysis. Exome sequencing, Seahorse respirometry in patient fibroblasts, mitochondrial membrane potential assays, citrate supplementation rescue experiments JIMD reports Medium 27306203
2018 SLC25A1 is upregulated in lung cancer stem cells (CSCs) and by hypoxia/reoxygenation stress and ionizing radiation. SLC25A1 maintains the mitochondrial pool of citrate and redox balance in CSCs; its inhibition (using BTA or CNASB) leads to reactive oxygen species accumulation, reduced mitochondrial metabolism, impaired DNA repair capacity, and inhibition of CSC self-renewal. SLC25A1 inhibition is synthetic lethal with cisplatin or EGFR inhibitor treatment. SLC25A1 inhibition with BTA/CNASB, CSC sphere assays, ROS measurement, clonogenic survival, xenograft models, metabolic profiling Cell death and differentiation High 29651165
2018 SLC25A1 upregulation by hypoxia/reoxygenation stress supports cellular and mitochondrial redox homeostasis and metabolic flexibility in cancer cells. Pharmacological inhibition of SLC25A1 disturbs redox balance, lowers mitochondrial metabolism, and radiosensitizes cancer cells by increasing ROS and reducing DNA repair capacity, particularly in chronically hypoxic tumor cells. SLC25A1 inhibition (BTA, CNASB), irradiation clonogenic assays, ROS measurement, DNA damage (γH2AX) assays, metabolic flux analysis in multiple cancer cell lines Frontiers in oncology Medium 29888201
2019 ADGRL4/ELTD1 silencing in endothelial cells induces transcriptional upregulation of SLC25A1 (and ACLY), altering the cellular metabolic profile. Affected metabolites include elevated cis-aconitic acid and depleted cytidine monophosphate, suggesting SLC25A1 participates in a metabolic regulatory circuit downstream of ADGRL4/ELTD1 in endothelial cells. siRNA silencing of ADGRL4/ELTD1 in HUVECs, transcriptional profiling, LC-MS metabolomics Metabolites Low 31775252
2020 Pharmacological inhibition of Slc25a1 with CTPI-2 in mouse models of NAFLD/NASH reverts steatosis, reduces inflammatory macrophage infiltration, mitigates obesity, and normalizes hyperglycemia. Mechanistically, Slc25a1 inhibition rewires the lipogenic program by blunting PPARγ signaling and inhibiting gluconeogenic gene expression via citrate-dependent activities. Liver-targeted Slc25a1 knockout recapitulates metabolic improvements, demonstrating tissue-specific functions. CTPI-2 pharmacological inhibition, global Slc25a1 heterozygous knockout, liver-targeted conditional Slc25a1 knockout, high-fat diet NASH model, lipid profiling, glucose tolerance tests, PPARγ and gluconeogenic gene expression analysis Cell death and differentiation High 31959914
2021 SLC25A1 knockdown in colorectal cancer cells inhibits G1/S cell cycle progression and induces apoptosis. SLC25A1 reprograms energy metabolism by: (1) increasing de novo lipid synthesis under normal conditions, and (2) increasing oxidative phosphorylation to protect against energy stress-induced apoptosis, demonstrating dual metabolic roles dependent on nutritional context. SLC25A1 knockdown and overexpression in CRC cells, cell cycle analysis, apoptosis assays, OXPHOS measurement, de novo lipogenesis assays, xenograft models Cell death & disease Medium 34839347
2022 Neuronal overexpression of SLC25A1 in mouse forebrain neurons increases steady-state levels of citrate and acetyl-CoA, produces an autistic-like behavioral phenotype with jumping stereotypy, disrupts white matter integrity with activated microglia, and alters synaptic plasticity and morphology. Quantitative acetyl-proteomic analysis reveals differential acetylation adaptations in hippocampus and cortex, linking SLC25A1-mediated citrate export to cytosolic acetyl-CoA availability and downstream protein acetylation in neurons. Transgenic mouse overexpression of SLC25A1 in forebrain neurons, behavioral testing, metabolomics (citrate, acetyl-CoA), MRI white matter integrity, electrophysiology, quantitative proteomics and acetyl-proteomics Brain : a journal of neurology High 35203088
2022 IL-1β stimulation induces translocation of IRAKM Myddosome to mitochondria, where IRAKM interacts with and phosphorylates the mitochondrial citrate carrier Slc25a1. This phosphorylation promotes IL-1β-induced mitochondrial citrate transport to the cytosol and drives de novo lipogenesis in adipocytes. The IRAKM-Slc25a1 axis also mediates IL-1β-induced PGC1α acetylation to regulate thermogenic gene expression. Adipocyte-specific IRAKM deficiency reduces high-fat diet-induced obesity. Co-immunoprecipitation of IRAKM with Slc25a1, kinase phosphorylation assays, adipocyte-specific IRAKM knockout mice, HFD obesity model, mitochondrial citrate transport assay, de novo lipogenesis measurement, acetylation assays Nature communications High 35585086
2023 KRASG12D upregulates SLC25A1 expression in pancreatic cancer via GLI1, which directly binds the SLC25A1 promoter to stimulate its transcription. Enhanced SLC25A1 expression increases cytosolic citrate, fatty acids, and key lipid metabolism enzymes. A high-fat diet further stimulates the KRASG12D-GLI1-SLC25A1 axis. Pharmacological inhibition of SLC25A1 or GLI1 significantly suppresses pancreatic tumorigenesis in KrasG12D/+ mice. ChIP demonstrating GLI1 binding to SLC25A1 promoter, genetically engineered KrasG12D mouse models, SLC25A1/GLI1 pharmacological inhibition, metabolomics (citrate, fatty acids), HFD tumor models Cancer research High 37695315
2023 Systemic overexpression of SLC25A1 in mice increases cytosolic citrate and acetyl-CoA but does not engage the ER acetylation machinery (SLC33A1) or cause premature death (unlike SLC13A5 overexpression), revealing that the directionality of citrate import (mitochondrial export via SLC25A1 vs. extracellular import via SLC13A5) produces fundamentally different biological responses and metabolic profiles despite both elevating cytosolic citrate. Transgenic mice with systemic SLC25A1 overexpression, comparative metabolomics with SLC13A5 transgenic mice, ER acetylation machinery analysis, phenotypic characterization Communications biology Medium 37689798
2023 SLC25A1 exports citrate from mitochondria to the cytosol, where ATP citrate lyase (ACLY) converts it to acetyl-CoA. This cytosolic acetyl-CoA sustains FSP1 acetylation at K168 (mediated by KAT2B and reversed by HDAC3), preventing FSP1 degradation via K29-linked ubiquitin chains and thus protecting cancer cells from ferroptosis. Pharmacological inhibition of SLC25A1 reduces FSP1 acetylation, promotes its proteasomal degradation, and enhances ferroptosis sensitivity both in vitro and in vivo. CRISPR-Cas9 screen of SLC superfamily, SLC25A1 inhibition (CTPI-2), ACLY inhibition, FSP1 acetylation and ubiquitination assays, site-directed mutagenesis (K168), KAT2B/HDAC3 identification, ferroptosis assays in vitro and xenograft models The EMBO journal High 39881208
2023 Parthenolide (PTL) inhibits SLC25A1 expression, causing ROS production, reduced oxidative phosphorylation, and mitochondrial dysfunction in liver cancer stem cells. SLC25A1 inhibition also decreases IDH2 expression and mitochondrial respiratory chain complex genes. The inhibitory effects of PTL on mitochondrial function and self-renewal are abolished by SLC25A1 knockdown or CTPI-2 treatment, demonstrating that PTL acts through SLC25A1-mediated mitochondrial function. RNA-seq, SLC25A1 knockdown, CTPI-2 inhibitor, ROS assay, OXPHOS measurement, mitochondrial membrane potential, sphere formation assays, in vivo xenograft Cell death discovery Medium 37741815

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2018 The shieldin complex mediates 53BP1-dependent DNA repair. Nature 502 30022168
2012 The mitochondrial transporter family SLC25: identification, properties and physiopathology. Molecular aspects of medicine 492 23266187
2012 Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget 462 22869205
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2012 Genome-wide association study identifies multiple loci influencing human serum metabolite levels. Nature genetics 436 22286219
2011 Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science (New York, N.Y.) 420 21817013
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2011 The mitochondrial citrate carrier: a new player in inflammation. The Biochemical journal 311 21787310
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
1995 Gating of the voltage-dependent chloride channel CIC-0 by the permeant anion. Nature 298 7845466
2009 Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell 281 19167051
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
1996 Biosynthesis of triacylglycerols. Progress in lipid research 231 8944226
2016 Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Molecular cell 220 27499296
2009 Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Science signaling 207 19738201
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
1997 CTP:phosphocholine cytidylyltransferase. Biochimica et biophysica acta 186 9370319
2017 The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs. Nature communications 176 28685749
2000 Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization. Trends in biochemical sciences 172 10973058
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2014 A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation. Biochimica et biophysica acta 163 25072865
2016 CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas. The American journal of surgical pathology 160 26685084
2009 Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. Gut 157 19240061
2010 A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. The EMBO journal 153 20186120
2020 AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System. Molecular cell 152 31995728
1993 The mitochondrial tricarboxylate transport protein. cDNA cloning, primary structure, and comparison with other mitochondrial transport proteins. The Journal of biological chemistry 143 8514800
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2019 ParB-type DNA Segregation Proteins Are CTP-Dependent Molecular Switches. Cell 126 31835030
2015 CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis. Progress in lipid research 115 26165797
2012 CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas. Acta neuropathologica 115 22588899
2013 Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. American journal of human genetics 114 23561848
2018 The mitochondrial citrate carrier, SLC25A1, drives stemness and therapy resistance in non-small cell lung cancer. Cell death and differentiation 112 29651165
2019 Self-organization of parS centromeres by the ParB CTP hydrolase. Science (New York, N.Y.) 105 31649139
2020 Inhibition of the mitochondrial citrate carrier, Slc25a1, reverts steatosis, glucose intolerance, and inflammation in preclinical models of NAFLD/NASH. Cell death and differentiation 98 31959914
2017 ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition. Cell reports 96 28178529
2017 CIC-DUX4 Induces Small Round Cell Sarcomas Distinct from Ewing Sarcoma. Cancer research 92 28404587
2007 Developmental and metabolic effects of disruption of the mouse CTP:phosphoethanolamine cytidylyltransferase gene (Pcyt2). Molecular and cellular biology 92 17325045
2008 Characterization of the yeast DGK1-encoded CTP-dependent diacylglycerol kinase. The Journal of biological chemistry 81 18458076
2014 Common regulatory control of CTP synthase enzyme activity and filament formation. Molecular biology of the cell 78 24920825
2014 CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 78 24947144
1989 CTP:phosphocholine cytidylyltransferase is a substrate for cAMP-dependent protein kinase in vitro. The Journal of biological chemistry 74 2536019
2014 CTP synthase forms cytoophidia in the cytoplasm and nucleus. Experimental cell research 73 24503052
2006 Defects in CTP:PHOSPHORYLETHANOLAMINE CYTIDYLYLTRANSFERASE affect embryonic and postembryonic development in Arabidopsis. The Plant cell 70 17189343
2014 Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. Journal of neuromuscular diseases 69 26870663
2017 CIC break-apart fluorescence in-situ hybridization misses a subset of CIC-DUX4 sarcomas: a clinicopathological and molecular study. Histopathology 67 28493604
2018 The Mitochondrial Citrate Carrier (SLC25A1) Sustains Redox Homeostasis and Mitochondrial Metabolism Supporting Radioresistance of Cancer Cells With Tolerance to Cycling Severe Hypoxia. Frontiers in oncology 65 29888201
2014 Ack kinase regulates CTP synthase filaments during Drosophila oogenesis. EMBO reports 64 25223282
2017 NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma. Human pathology 63 28188754
2016 The Interplay between Myc and CTP Synthase in Drosophila. PLoS genetics 63 26889675
1993 Expression, purification, and characterization of CTP:glycerol-3-phosphate cytidylyltransferase from Bacillus subtilis. The Journal of biological chemistry 63 8393871
2018 The Tumor Suppressor CIC Directly Regulates MAPK Pathway Genes via Histone Deacetylation. Cancer research 59 29844126
2019 CIC-DUX4 oncoprotein drives sarcoma metastasis and tumorigenesis via distinct regulatory programs. The Journal of clinical investigation 56 31329165
2011 An ana2/ctp/mud complex regulates spindle orientation in Drosophila neuroblasts. Developmental cell 56 21920316
1996 Isolation and characterization of ECT1 gene encoding CTP: phosphoethanolamine cytidylyltransferase of Saccharomyces cerevisiae. Journal of biochemistry 56 8982874
1995 Phosphorylation of CTP synthetase from Saccharomyces cerevisiae by protein kinase C. The Journal of biological chemistry 55 7797479
1999 CTP:phosphocholine cytidylyltransferase: insights into regulatory mechanisms and novel functions. Biochemical and biophysical research communications 54 10208837
2017 Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines. Scientific reports 53 28680140
2009 A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity. Human molecular genetics 52 19654186
2013 Only one isoform of Drosophila melanogaster CTP synthase forms the cytoophidium. PLoS genetics 50 23459760
2021 SLC25A1 promotes tumor growth and survival by reprogramming energy metabolism in colorectal cancer. Cell death & disease 49 34839347
2013 Loss of CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 48 24030748
1977 Asymmetry of binding and physical assignments of CTP and ATP sites in aspartate transcarbamoylase. The Journal of biological chemistry 48 334776
2019 Drosophila CTP synthase can form distinct substrate- and product-bound filaments. Journal of genetics and genomics = Yi chuan xue bao 47 31902586
2021 Relief of ParB autoinhibition by parS DNA catalysis and recycling of ParB by CTP hydrolysis promote bacterial centromere assembly. Science advances 46 34613769
2021 CTP promotes efficient ParB-dependent DNA condensation by facilitating one-dimensional diffusion from parS. eLife 45 34250901
2018 Characterization of filament-forming CTP synthases from Arabidopsis thaliana. The Plant journal : for cell and molecular biology 45 30030857
1996 Regulation of yeast CTP synthetase activity by protein kinase C. The Journal of biological chemistry 45 8626655
2015 Molecular background of oligodendroglioma: 1p/19q, IDH, TERT, CIC and FUBP1. CNS oncology 44 26545048
2021 A CTP-dependent gating mechanism enables ParB spreading on DNA. eLife 43 34397383
1994 Purification and characterization of CTP synthetase, the product of the URA7 gene in Saccharomyces cerevisiae. Biochemistry 43 8075080
2016 Ewing sarcoma and the new emerging Ewing-like sarcomas: (CIC and BCOR-rearranged-sarcomas). A systematic review. Histology and histopathology 42 27306060
1994 Primary structure and expression of a human CTP:phosphocholine cytidylyltransferase. Biochimica et biophysica acta 42 7918629
2015 Regulation of CTP Synthase Filament Formation During DNA Endoreplication in Drosophila. Genetics 41 26482795
2021 CTP-controlled liquid-liquid phase separation of ParB. Journal of molecular biology 40 34902429
2003 Enhanced expression and activation of CTP:phosphocholine cytidylyltransferase beta2 during neurite outgrowth. The Journal of biological chemistry 40 12928431
2005 CIC, a gene involved in cerebellar development and ErbB signaling, is significantly expressed in medulloblastomas. Journal of neuro-oncology 36 15981098
2001 CTP:phosphocholine cytidylyltransferase, a new sterol- and SREBP-responsive gene. Journal of lipid research 36 11483628
2023 Expanding the Molecular Diversity of CIC-Rearranged Sarcomas With Novel and Very Rare Partners. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 35 36788092
2015 ETV/Pea3 family transcription factor-encoding genes are overexpressed in CIC-mutant oligodendrogliomas. Genes, chromosomes & cancer 34 26357005
1999 Identification of Ser424 as the protein kinase A phosphorylation site in CTP synthetase from Saccharomyces cerevisiae. Biochemistry 34 10393561
2018 Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase. Cell reports 33 30184506
2019 Undifferentiated round cell sarcomas with CIC-DUX4 gene fusion: expanding the clinical spectrum. Pathology 32 31870501
2018 Transcriptomic analysis of CIC and ATXN1L reveal a functional relationship exploited by cancer. Oncogene 30 30093628
2007 Calmodulin binds and stabilizes the regulatory enzyme, CTP: phosphocholine cytidylyltransferase. The Journal of biological chemistry 29 17804406
1984 Trifluoperazine and chlorpromazine inhibit phosphatidylcholine biosynthesis and CTP:phosphocholine cytidylyltransferase in HeLa cells. Biochimica et biophysica acta 28 6089904
2021 CTP regulates membrane-binding activity of the nucleoid occlusion protein Noc. Molecular cell 26 34270916
2020 DNA Methylation Profiling for Diagnosing Undifferentiated Sarcoma with Capicua Transcriptional Receptor (CIC) Alterations. International journal of molecular sciences 26 32155762
2014 Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment. Journal of inherited metabolic disease 26 24687295
1997 CTP:phosphoethanolamine cytidylyltransferase. Biochimica et biophysica acta 26 9370320
2020 Radiomics Features Predict CIC Mutation Status in Lower Grade Glioma. Frontiers in oncology 25 32676453
2023 Oncogenic KRASG12D Reprograms Lipid Metabolism by Upregulating SLC25A1 to Drive Pancreatic Tumorigenesis. Cancer research 24 37695315
2005 Interdomain and membrane interactions of CTP:phosphocholine cytidylyltransferase revealed via limited proteolysis and mass spectrometry. The Journal of biological chemistry 24 15713672
2023 A novel SLC25A1 inhibitor, parthenolide, suppresses the growth and stemness of liver cancer stem cells with metabolic vulnerability. Cell death discovery 23 37741815
2022 Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 23 35440765
2020 Making heads or tails - the emergence of capicua (CIC) as an important multifunctional tumour suppressor. The Journal of pathology 23 32073140
2001 CTP:phosphocholine cytidylyltransferase inhibition by ceramide via PKC-alpha, p38 MAPK, cPLA2, and 5-lipoxygenase. American journal of physiology. Lung cellular and molecular physiology 22 11404253
1990 CTP:phosphocholine cytidylyltransferase in rat lung: relationship between cytosolic and membrane forms. Biochimica et biophysica acta 22 2164421
2019 ADGRL4/ELTD1 Silencing in Endothelial Cells Induces ACLY and SLC25A1 and Alters the Cellular Metabolic Profile. Metabolites 21 31775252
2010 Complementation of the metabolic defect in CTP:phosphoethanolamine cytidylyltransferase (Pcyt2)-deficient primary hepatocytes. Metabolism: clinical and experimental 21 20427062
1996 Chlamydia trachomatis CTP synthetase: molecular characterization and developmental regulation of expression. Molecular microbiology 21 8951811
2025 SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation. The EMBO journal 20 39881208
2022 A case of CIC-rearranged sarcoma with CIC-LEUTX gene fusion in spinal cord. Neuropathology : official journal of the Japanese Society of Neuropathology 20 35859319
2020 Advances into Understanding the Vital Role of the Mitochondrial Citrate Carrier (CIC) in Metabolic Diseases. Pharmacological research 20 32814170
2017 Critical roles of CTP synthase N-terminal in cytoophidium assembly. Experimental cell research 20 28342900
1999 Cloning and expression of CTP:phosphoethanolamine cytidylyltransferase cDNA from rat liver. The Biochemical journal 20 10493918
2023 CIC reduces xCT/SLC7A11 expression and glutamate release in glioma. Acta neuropathologica communications 19 36647117
2023 Differential roles of CTP synthetases CTPS1 and CTPS2 in cell proliferation. Life science alliance 19 37348953
2016 Severe Neonatal Presentation of Mitochondrial Citrate Carrier (SLC25A1) Deficiency. JIMD reports 19 27306203
2023 CTP switches in ParABS-mediated bacterial chromosome segregation and beyond. Current opinion in microbiology 18 36871427
2022 Increased expression of SLC25A1/CIC causes an autistic-like phenotype with altered neuron morphology. Brain : a journal of neurology 18 35203088
2022 Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of CIC-rearranged sarcoma. Genes, chromosomes & cancer 18 35715887
2021 The CAM Model for CIC-DUX4 Sarcoma and Its Potential Use for Precision Medicine. Cells 18 34685592
2012 Mechanism of hypertriglyceridemia in CTP:phosphoethanolamine cytidylyltransferase-deficient mice. Journal of lipid research 18 22764088
2004 Membrane lipid biosynthesis in Chlamydomonas reinhardtii: expression and characterization of CTP:phosphoethanolamine cytidylyltransferase. The Biochemical journal 18 15147238
2022 WEE1 kinase is a therapeutic vulnerability in CIC-DUX4 undifferentiated sarcoma. JCI insight 17 35315355
2022 IL-1R-IRAKM-Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet-induced obesity in mice. Nature communications 17 35585086
2020 Membrane Lipids Assist Catalysis by CTP: Phosphocholine Cytidylyltransferase. Journal of molecular biology 17 32234309
2022 CIC rearranged sarcomas: A single institution experience of the potential pitfalls in interpreting CIC FISH results. Pathology, research and practice 16 35093696
1998 Enzymatic incorporation of 2'-thio-CTP into the HDV ribozyme. RNA (New York, N.Y.) 16 9510335
2023 The citrate transporters SLC13A5 and SLC25A1 elicit different metabolic responses and phenotypes in the mouse. Communications biology 15 37689798