Affinage

CPT1C

Palmitoyl thioesterase CPT1C · UniProt Q8TCG5

Length
803 aa
Mass
91.0 kDa
Annotated
2026-06-09
36 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 11/11 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CPT1C is a brain-enriched, malonyl-CoA-responsive endoplasmic reticulum protein that couples cellular energy and nutrient status to neuronal lipid signaling, synaptic receptor trafficking, and organelle transport (PMID:18192268, PMID:31868590). Although it retains weak carnitine palmitoyltransferase activity toward palmitoyl-CoA, its catalytic efficiency is 20–300 times lower than CPT1A, and it localizes to the ER rather than mitochondria, distinguishing it functionally from canonical CPT1 isoforms (PMID:18192268). CPT1C operates as a low-efficiency palmitoyl thioesterase, using a Ser252/His470/Asp474 catalytic triad to depalmitoylate the AMPA receptor subunit GluA1 and thereby control its surface delivery (PMID:30135643). It physically interacts with GluA1 and GluA2 and promotes AMPAR-mediated synaptic transmission by driving de novo, mTOR-dependent GluA1 synthesis and by enhancing surface receptor number through the palmitoylable GluA1 residue C585 (PMID:26338711, PMID:25698923). CPT1C transduces malonyl-CoA levels into receptor trafficking decisions by inhibiting the PI(4)P phosphatase SAC1: when malonyl-CoA is high CPT1C restrains SAC1 to support GluA1 surface delivery, while glucose deprivation releases this inhibition, depletes TGN PI(4)P, and retains GluA1 intracellularly (PMID:32931550). In parallel, CPT1C binds the ER protein protrudin to facilitate transfer of Kinesin-1 onto late endosomes/lysosomes, promoting their anterograde transport and axon elongation in a malonyl-CoA- and AMPK-dependent manner (PMID:31868590). Consistent with these synaptic roles, CPT1C-deficient mice show impaired CA3-CA1 long-term potentiation, defective dendritic spine maturation, and learning and memory deficits (PMID:37309891). In the hypothalamus CPT1C acts downstream of AMPK to regulate ceramide and endocannabinoid metabolism, controlling ghrelin-induced feeding and leptin/diet-induced brown adipose tissue thermogenesis (PMID:23493572, PMID:30448371, PMID:40268191). CPT1C translation is itself gated by a 5′ UTR upstream ORF that is de-repressed by glucose deprivation, palmitate, and AMPK inhibition, embedding the protein within an energy-sensing feedback loop (PMID:21961029). In cancer cells CPT1C is transcriptionally driven by ERRα and YY1 and remodels lipid metabolism—supporting autophagy-dependent survival under glucose deprivation, lipid droplet biogenesis, plasma-membrane lipid saturation, and the stearate/oleate balance—while its abundance is restricted by APC/C-mediated degradation across the cell cycle (PMID:29725060, PMID:32641987, PMID:38996932, PMID:38783346, PMID:36674468, PMID:37151873). A missense CPT1C mutation (p.Cys37Arg) that perturbs protein conformation and reduces lipid droplets is linked to hereditary spastic paraplegia, consistent with its interaction with atlastin-1 (PMID:25751282).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2007 Medium

    Establishing where CPT1C acts and whether it influences whole-body energy balance was the first question; its CNS-wide neuronal expression and the protection from diet-induced weight gain on hypothalamic overexpression positioned it as a neuronal regulator of feeding.

    Evidence Immunohistochemistry, mitochondrial fractionation, and stereotactic adenoviral overexpression with body-weight monitoring in mice

    PMID:17559810

    Open questions at the time
    • Reported mitochondrial localization was later contradicted by ER localization
    • Mechanism linking CPT1C to feeding not defined
    • No molecular activity assigned
  2. 2008 High

    Defining the biochemical identity of CPT1C resolved its subcellular home and showed it is a poor carnitine palmitoyltransferase, implying its physiological role is not bulk fatty acid oxidation.

    Evidence GFP-fusion live imaging, brain subcellular fractionation, HPLC-MS acylcarnitine profiling, and microsomal CPT1 kinetic assays in PC-12 cells

    PMID:18192268

    Open questions at the time
    • Physiological substrate and true catalytic function unresolved
    • Reconciliation with prior mitochondrial localization claim incomplete
    • No interacting partners identified
  3. 2009 High

    Whole-body knockout revealed that loss of CPT1C worsens diet-induced insulin resistance with tissue-level metabolic deficits, demonstrating a systemic metabolic function despite CNS-restricted expression.

    Evidence CPT1C KO mice with glucose/insulin tolerance tests, hepatic gluconeogenesis and muscle glucose uptake assays, and compensatory CPT1A/CPT1B expression measurement

    PMID:19224198

    Open questions at the time
    • Peripheral phenotypes are indirect consequences of central deficiency
    • Molecular mechanism not addressed
    • Compensatory isoform upregulation complicates interpretation
  4. 2011 Medium

    Discovery of a 5′ UTR uORF that represses CPT1C translation, relieved by nutrient stress and AMPK inhibition, established that CPT1C abundance is wired to cellular energy status.

    Evidence 5′ UTR luciferase reporter constructs under glucose deprivation, palmitate, and AMPK inhibitor treatment

    PMID:21961029

    Open questions at the time
    • In vitro reporter only, single lab
    • Endogenous translational regulation not demonstrated
    • Trans-acting factors binding the uORF unknown
  5. 2013 High

    Genetic and pharmacological dissection placed CPT1C in the ghrelin-AMPK-ceramide feeding circuit, providing a mechanistic link between CPT1C and orexigenic signaling.

    Evidence CPT1C KO mice with intracerebroventricular ghrelin, ceramide-synthesis inhibitor, and ceramide rescue, plus neuropeptide and ceramide measurements

    PMID:23493572

    Open questions at the time
    • How CPT1C controls ceramide levels enzymatically unclear
    • Direct molecular target downstream of CPT1C not identified
  6. 2015 High

    Identifying CPT1C as a physical and functional partner of AMPAR subunits established a synaptic role distinct from metabolism, showing it promotes de novo GluA1 synthesis and surface delivery without altering receptor biophysics.

    Evidence Reciprocal Co-IP, mEPSC electrophysiology in KO neurons, metabolic labeling for synthesis, surface biotinylation, and GluA1 C585 mutagenesis in neurons and heterologous cells

    PMID:25698923 PMID:26338711

    Open questions at the time
    • Molecular activity of CPT1C on GluA1 not yet defined
    • Mechanism of mTOR-dependent synthesis enhancement unknown
    • Link between metabolism and AMPAR regulation unresolved
  7. 2015 Medium

    Linking a CPT1C missense mutation and an atlastin-1 interaction to reduced lipid droplets connected CPT1C to hereditary spastic paraplegia and to lipid droplet biogenesis.

    Evidence Whole-exome sequencing, Co-IP with atlastin-1, NMR conformational analysis of the C37R mutant, and lipid droplet quantification in cells and KO neurons

    PMID:25751282

    Open questions at the time
    • Causality of the mutation in disease from a single family
    • Mechanism connecting CPT1C to lipid droplet formation unresolved
    • Functional role of atlastin-1 interaction undefined
  8. 2018 Medium

    Catalytic-triad mutagenesis assigned a palmitoyl thioesterase activity to CPT1C and showed that depalmitoylation of GluA1 underlies its trafficking effect, defining the molecular mechanism behind the AMPAR phenotype.

    Evidence In silico triad prediction, S252A/H470A/D474A mutagenesis, acyl-RAC palmitoylation assay, surface biotinylation, and electrophysiology in neurons

    PMID:30135643

    Open questions at the time
    • Thioesterase activity demonstrated indirectly via mutants, single lab
    • Full substrate repertoire beyond GluA1 unknown
    • Relationship to weak acyltransferase activity unclear
  9. 2018 High

    VMH-specific epistasis experiments placed CPT1C downstream of AMPK in controlling brown adipose tissue thermogenesis, extending its hypothalamic role from feeding to energy expenditure.

    Evidence CPT1C KO and VMH AMPK double knockout mice, icv leptin, BAT thermogenesis readouts, and VMH-specific viral CPT1C rescue

    PMID:30448371

    Open questions at the time
    • Molecular effector linking CPT1C to UCP1 induction not defined
    • Lipid species mediating the signal not identified
  10. 2019 High

    The protrudin-Kinesin-1 mechanism showed CPT1C acts as a malonyl-CoA sensor governing anterograde lysosome/endosome transport and axon growth, unifying its energy-sensing and trafficking functions.

    Evidence Co-IP and Kinesin-1 transfer assays, live-cell LE/Lys transport imaging in HeLa and cortical neurons, AMPK activation, malonyl-CoA inhibition, and axon length measurement

    PMID:31868590

    Open questions at the time
    • Structural basis of malonyl-CoA sensing not resolved
    • Whether thioesterase activity is involved in transport unclear
  11. 2020 High

    Identifying SAC1 as a CPT1C-regulated PI(4)P phosphatase provided the mechanistic bridge between malonyl-CoA status and GluA1 trafficking through ER-TGN contact sites.

    Evidence Metabolic stress in cortical neurons, SAC1 activity assay, PI(4)P quantification, GluA1 surface biotinylation, SAC1 localization imaging, and malonyl-CoA measurement

    PMID:32931550

    Open questions at the time
    • Direct physical regulation of SAC1 by CPT1C not structurally defined
    • Single lab
  12. 2020 Medium

    Transcriptional control of CPT1C by ERRα, modulated by miR-1291, established that CPT1C expression is regulated to support cancer cell proliferation and metabolism.

    Evidence Luciferase reporter, ChIP, expression assays, proliferation/cell-cycle/ATP/ROS readouts, and xenograft model

    PMID:32641987

    Open questions at the time
    • Direct metabolic mechanism in tumors not dissected
    • Single lab
    • Generality across cancer types untested
  13. 2018 Medium

    Overexpression in mesenchymal stem cells revealed an FAO-independent, autophagy- and lipolysis-dependent survival function under glucose deprivation, expanding CPT1C beyond neurons into stress-adaptive metabolism.

    Evidence CPT1C overexpression in hMSCs, viability under glucose/oxygen deprivation, FAO assay, autophagy and lipolysis inhibitor treatment, lipid droplet and ATP measurement

    PMID:29725060

    Open questions at the time
    • Mechanism connecting CPT1C to autophagy induction unknown
    • Overexpression model may not reflect endogenous role
  14. 2023 Medium

    Lipidomic and flux studies in breast cancer cells tied CPT1C to plasma membrane lipid saturation, drug uptake/anthracycline resistance, and the stearate/oleate balance controlling senescence, defining its lipid-remodeling role in cancer.

    Evidence CPT1C silencing, LC-HRMS lipidomics, 13C-metabolic flux analysis, drug uptake/viability assays, fatty acid supplementation, SCD-1 inhibition, and senescence assays

    PMID:36674468 PMID:37151873

    Open questions at the time
    • Enzymatic basis of CPT1C-dependent lipid remodeling unresolved
    • Single cell line for each phenotype
    • Direct vs indirect effects on membrane composition unclear
  15. 2024 Medium

    Identification of CPT1C as an APC/C substrate and a YY1/hypoxia-regulated gene showed that its abundance is cell-cycle- and stress-controlled to drive tumor proliferation.

    Evidence Cell cycle synchronization, PLA and Co-IP with APC/C, YY1 knockdown and CPT1C CRISPR KO epistasis, metabolic assays, and xenograft models

    PMID:38783346 PMID:38996932

    Open questions at the time
    • APC/C degron and adaptor specificity not mapped
    • Direct YY1 promoter binding inferred
    • Single lab for each
  16. 2026 Medium

    Cell-type-specific work in the nucleus accumbens connected CPT1C-mediated GluA1 depalmitoylation and mTORC1 disinhibition via TSC2 to stress-induced depressive behavior and antidepressant response, generalizing the AMPAR mechanism to behavior.

    Evidence D1/D2-MSN-specific CPT1C knockdown, GluA1 depalmitoylation assay, chronic stress model, behavioral and synaptic plasticity recording, and TSC2/mTORC1 analysis

    PMID:41741705

    Open questions at the time
    • Not independently replicated
    • Mechanism of TSC2 targeting not biochemically defined
    • Cell-type-specific circuit logic incompletely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CPT1C's weak acyltransferase activity, palmitoyl thioesterase activity, and malonyl-CoA sensing are integrated into a single biochemical mechanism—and what structural features underlie SAC1 inhibition, protrudin binding, and substrate recognition—remains unresolved.
  • No structural model of CPT1C bound to malonyl-CoA, GluA1, SAC1, or protrudin
  • Full physiological substrate repertoire of the thioesterase activity undefined
  • Whether catalytic and sensing functions are mechanistically coupled is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 2 GO:0016740 transferase activity 1 GO:0098772 molecular function regulator activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 3 R-HSA-9609507 Protein localization 2 R-HSA-1640170 Cell Cycle 1
Partners
ANKRD13ATL1ESRRAGRIA1GRIA2SACM1LYY1ZFYVE27

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 CPT1C localizes to the endoplasmic reticulum (not mitochondria) of neurons, with its N-terminal region responsible for ER localization. It has carnitine palmitoyltransferase activity toward palmitoyl-CoA as substrate, producing palmitoylcarnitine, but with 20–300 times lower catalytic efficiency than CPT1A. GFP-fusion overexpression and live-cell imaging, subcellular fractionation/Western blot from mouse brain, HPLC-MS acylcarnitine profiling in PC-12 cells, microsomal CPT1 activity assays with kinetic analysis The Journal of biological chemistry High 18192268
2007 CPT1C is widely expressed in neurons throughout the CNS including hypothalamic feeding centers, where it localizes as an outer integral membrane protein of mitochondria (this localization differs from the 2008 ER finding). Ectopic over-expression of CPT1C in the hypothalamus via stereotactic adenoviral injection protects mice from high-fat diet-induced weight gain. Immunohistochemistry, mitochondrial fractionation, stereotactic adenoviral injection with body weight monitoring in mice Biochemical and biophysical research communications Medium 17559810
2013 CPT1C in the hypothalamus is required for the orexigenic action of ghrelin. Ghrelin signaling upregulates hypothalamic C18:0 ceramide levels in a CPT1C-dependent manner, and central ceramide synthesis inhibition blocks ghrelin-induced feeding; central ceramide administration rescues food intake in CPT1C KO mice. CPT1C knockout mouse model, intracerebroventricular drug administration (ghrelin, myriocin, ceramide), neuropeptide expression analysis (AgRP, NPY), ceramide level measurement Diabetes High 23493572
2009 CPT1C KO mice develop more severe high-fat diet-induced insulin resistance than wild-type, attributable to elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake, associated with reduced fatty acid oxidation in those tissues. CPT1C deletion also causes compensatory elevation of hypothalamic CPT1A and CPT1B expression and activity, partly induced by elevated plasma NEFA. CPT1C knockout mouse model, glucose/insulin tolerance tests, hepatic gluconeogenesis assays, skeletal muscle glucose uptake, gene expression and activity assays in liver and muscle Diabetologia High 19224198
2011 The CPT1C 5′ UTR contains an upstream open reading frame (uORF) that represses translation from the main ORF. This repression is relieved by glucose deprivation and palmitate-BSA treatment, and AMPK inhibition also relieves uORF-dependent repression, linking nutrient/energy status to CPT1C translational regulation. 5′ UTR/luciferase reporter constructs, sequence analysis, glucose deprivation and palmitate treatment, AMPK inhibitor treatment PloS one Medium 21961029
2015 CPT1C physically interacts with AMPAR subunits GluA1 and GluA2, shares the same expression profile during neuronal maturation, and is required for normal AMPAR-mediated miniature excitatory postsynaptic currents and synaptic levels of GluA1 and GluA2. CPT1C promotes de novo synthesis (not degradation) of GluA1 post-transcriptionally and is required for mTOR-dependent GluA1 synthesis after chemical LTD and BDNF treatment. Co-immunoprecipitation, electrophysiology (mEPSC recording in CPT1C KO neurons), synaptic fractionation/Western blot, metabolic labeling for protein synthesis, CPT1C KO mouse neurons The Journal of biological chemistry High 26338711
2015 CPT1C is an interacting protein of AMPARs confirmed in heterologous expression systems; it enhances whole-cell currents of GluA1 homomeric and GluA1/GluA2 heteromeric receptors by increasing surface GluA1 receptor number, without altering AMPAR biophysical properties. CPT1C and AMPARs co-localize intracellularly (ER) but not at the plasma membrane. The palmitoylable residue C585 of GluA1 is important for CPT1C-mediated AMPAR trafficking enhancement. Co-immunoprecipitation in heterologous cells, whole-cell patch-clamp electrophysiology, surface biotinylation assay, co-localization imaging, mutagenesis of GluA1 C585 Frontiers in cellular neuroscience High 25698923
2015 CPT1C interacts with atlastin-1 (ATL1), an ER protein encoded by a gene mutated in pure HSPs. A missense CPT1C mutation (c.109C>T, p.Cys37Arg) alters protein conformation (by NMR) and reduces the number and size of lipid droplets on overexpression; CPT1C KO neurons also show reduced lipid droplets, suggesting a role in lipid droplet biogenesis. Whole-exome sequencing, Sanger sequencing, Co-immunoprecipitation (CPT1C–atlastin-1), NMR spectroscopy, lipid droplet quantification in cells and KO neurons JAMA neurology Medium 25751282
2018 CPT1C depalmitoylates GluA1: predicted catalytic triad residues Ser252, His470, and Asp474 are required for CPT1C's palmitoyl thioesterase (PTE) activity. Mutation of His470 (H470A) abolishes CPT1C-dependent depalmitoylation of GluA1 and eliminates the increase in GluA1 surface expression. The effect is ER-specific and isoform-specific. In silico catalytic triad prediction, site-directed mutagenesis of CPT1C (S252A, H470A, D474A), palmitoylation state assay (acyl-RAC), surface biotinylation, electrophysiology in neurons Frontiers in molecular neuroscience Medium 30135643
2018 CPT1C in the ventromedial hypothalamus (VMH) is necessary for leptin- and high-fat diet-induced brown adipose tissue (BAT) thermogenesis activation. CPT1C acts downstream of AMPK in the VMH: genetic inactivation of AMPK in the VMH fails to induce BAT thermogenesis and body weight loss in CPT1C KO mice. Restoration of CPT1C expression in the VMH rescues the thermogenic phenotype. CPT1C KO mice, VMH-specific AMPK knockout, intracerebroventricular leptin administration, BAT thermogenesis measurement (UCP1, temperature), VMH-specific CPT1C viral rescue Molecular metabolism High 30448371
2019 CPT1C senses malonyl-CoA and promotes anterograde transport of late endosomes/lysosomes (LE/Lys) by interacting with the ER protein protrudin, facilitating transfer of Kinesin-1 from protrudin to LE/Lys. In cortical neurons, glucose deprivation, AMPK activation, or inhibition of malonyl-CoA synthesis decreases LE/Lys abundance at axon terminals and shortens axon length in a CPT1C-dependent manner. Co-immunoprecipitation (CPT1C–protrudin, Kinesin-1 transfer assay), live-cell imaging of LE/Lys transport in HeLa cells and mouse cortical neurons, CPT1C KD, AMPK pharmacological activation, malonyl-CoA synthesis inhibition, axon length measurement eLife High 31868590
2020 CPT1C regulates GluA1 AMPAR trafficking through the PI(4)P phosphatase SAC1. Under normal malonyl-CoA levels, CPT1C inhibits SAC1 catalytic activity, supporting GluA1 surface delivery. Under low malonyl-CoA (e.g., glucose deprivation), CPT1C-dependent inhibition of SAC1 is released, SAC1 translocates to ER-TGN contact sites, depletes TGN PI(4)P, and retains GluA1 at the TGN. Metabolic stress paradigms in cortical neurons, SAC1 activity assay, PI(4)P quantification, GluA1 surface biotinylation, SAC1 localization imaging (ER-TGN contact sites), malonyl-CoA level measurement The Journal of cell biology High 32931550
2018 CPT1C overexpression in human mesenchymal stem cells (hMSCs) promotes survival under glucose deprivation by enhancing autophagy, leading to increased lipid droplets and elevated intracellular ATP. This is independent of fatty acid oxidation. Inhibition of autophagy or lipolysis completely blocks CPT1C's protective effects. CPT1C overexpression in hMSCs, cell viability assays under glucose/oxygen deprivation, FAO assay, autophagy inhibitor treatment, lipolysis inhibitor treatment, lipid droplet staining, ATP measurement Scientific reports Medium 29725060
2020 ERRα (estrogen-related receptor α) is a transcription factor that directly activates CPT1C transcription. miR-1291 targets ERRα, thereby indirectly reducing CPT1C expression. CPT1C mediates effects of the miR-1291-ERRα axis on cancer cell proliferation and metabolism. Luciferase reporter assay (miR-1291 targeting ERRα 3′UTR), ChIP assay (ERRα binding to CPT1C promoter), RT-qPCR/Western blot, BrdU/colony formation/cell cycle assays, ATP/ROS measurements, xenograft tumor model Theranostics Medium 32641987
2024 YY1 directly activates transcription of CPT1C under hypoxic conditions in pancreatic cancer cells. YY1 and CPT1C synergistically regulate cell proliferation and metabolism (ATP levels, mitochondrial membrane potential, lipid content) under hypoxia. YY1 siRNA knockdown, CRISPR/Cas9 CPT1C knockout, double-knockdown rescue experiments, luciferase reporter or ChIP (implied by 'directly activated'), cellular metabolic assays Biochemical pharmacology Medium 38996932
2024 CPT1C is a substrate of the APC/C ubiquitin ligase complex: CPT1C protein levels fluctuate in a cell cycle-dependent manner, peaking at the G1/S boundary, and APC/C-mediated degradation controls its abundance. Elevated CPT1C accelerates G1/S transition and promotes tumor cell proliferation in vitro and in vivo. Cell cycle synchronization, proximity ligation assay and Co-immunoprecipitation (CPT1C–APC/C), immunoblotting, flow cytometry, MTS/scratch/transwell assays, xenograft transplantation Cell communication and signaling : CCS Medium 38783346
2023 CPT1C silencing in breast cancer cells (MDA-MB-231) increases plasma membrane phospholipid saturation (increased PM rigidity), reduces doxorubicin uptake, and confers anthracycline resistance. These changes are associated with CPT1C-dependent lipidome remodeling. CPT1C siRNA silencing, LC-HRMS lipidomics of PM-enriched fractions, drug uptake assays, cell viability assays International journal of molecular sciences Medium 36674468
2023 CPT1C knockdown induces cellular senescence in MDA-MB-231 cells accompanied by decreased stearate synthesis and increased oleate. Exogenous stearate inhibits proliferation, while oleate reverses CPT1C-knockdown-induced senescence. Inhibition of SCD-1 (stearoyl-CoA desaturase 1) phenocopies stearate-induced proliferation inhibition, placing CPT1C upstream of the stearate/oleate balance. 13C-metabolic flux analysis, CPT1C knockdown, exogenous fatty acid supplementation, SCD-1 inhibitor treatment, senescence assays International journal of biological sciences Medium 37151873
2025 CPT1C in SF1 neurons of the VMH is required for early caloric intake adjustment and melanocortin system activation upon high-fat diet exposure. CPT1C deficiency in SF1 neurons elevates hypothalamic endocannabinoid (eCB) levels under both chow and HFD conditions, which is proposed to reduce VMH activation by fatty acids and impair SF1-POMC drive upon fat intake. SF1-neuron-specific CPT1C conditional knockout mice, HFD feeding experiments, melanocortin pathway activation assays, endocannabinoid level measurement in hypothalamus, metabolic gene expression in peripheral tissues Molecular metabolism Medium 40268191
2026 CPT1C depalmitoylates GluA1 in the nucleus accumbens; enhanced GluA1 depalmitoylation mediates chronic stress-induced depressive-like behaviors. D2-MSN-specific CPT1C knockdown prevents stress-induced depression, while CPT1C deficiency in D1-MSNs abolishes fluoxetine's behavioral and synaptic effects. CPT1C also promotes GluA1 synthesis by disinhibiting mTORC1 via targeting tuberous sclerosis complex 2 (TSC2). Cell-type-specific (D1-MSN/D2-MSN) CPT1C knockdown, GluA1 depalmitoylation assay, chronic stress mouse model, behavioral assays, mTORC1 signaling analysis (TSC2 interaction), synaptic plasticity recording Molecular psychiatry Medium 41741705
2026 Fenofibrate activates PPARα, which transcriptionally upregulates CPT1C; CPT1C mediates fenofibrate's ability to restore mitochondrial function in senescent cells. Fenofibrate cannot reverse aging in Pparα−/− mice, establishing PPARα-dependence of the CPT1C upregulation. PPARα KO mice, D-galactose aging model, SAMP8 mice, lipidomic profiling, metabolic analyses of mitochondrial function, CPT1C expression analysis Pharmacological research Medium 41765248
2023 CPT1C is required for synaptic plasticity at the CA3-CA1 synapse: CPT1C KO mice show impaired long-term potentiation, reduced cortical γ oscillations, and deficits in hippocampal dendritic spine maturation, alongside motor learning, spatial memory, and habituation memory deficits. CPT1C KO mice, in vivo and ex vivo electrophysiology (LTP at CA3-CA1), cortical oscillation recording (EEG), dendritic spine morphology analysis, behavioral testing battery The Journal of physiology Medium 37309891

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 CPT1c is localized in endoplasmic reticulum of neurons and has carnitine palmitoyltransferase activity. The Journal of biological chemistry 157 18192268
2013 Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin. Diabetes 85 23493572
2015 Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia. JAMA neurology 65 25751282
2012 Molecular pathways: tumor cells Co-opt the brain-specific metabolism gene CPT1C to promote survival. Clinical cancer research : an official journal of the American Association for Cancer Research 55 22952346
2009 Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by a high-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake. Diabetologia 54 19224198
2010 Hypothalamic malonyl-CoA and CPT1c in the treatment of obesity. The FEBS journal 53 21199367
2014 High grade glioblastoma is associated with aberrant expression of ZFP57, a protein involved in gene imprinting, and of CPT1A and CPT1C that regulate fatty acid metabolism. Cancer biology & therapy 51 24618825
2020 A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis. Theranostics 45 32641987
2020 Enhanced fatty acid oxidation mediated by CPT1C promotes gastric cancer progression. Journal of gastrointestinal oncology 40 32953153
2022 MicroRNA-377-3p inhibits hepatocellular carcinoma growth and metastasis through negative regulation of CPT1C-mediated fatty acid oxidation. Cancer & metabolism 39 35057851
2007 Localization and effect of ectopic expression of CPT1c in CNS feeding centers. Biochemical and biophysical research communications 39 17559810
2018 CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity. Molecular metabolism 34 30448371
2018 CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy. Scientific reports 33 29725060
2015 AMPAR interacting protein CPT1C enhances surface expression of GluA1-containing receptors. Frontiers in cellular neuroscience 33 25698923
2017 Cpt1c regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions. Journal of Cancer 32 29151954
2020 Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking. The Journal of cell biology 30 32931550
2019 Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth. eLife 29 31868590
2015 Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus. The Journal of biological chemistry 29 26338711
2023 To be or not to be a fat burner, that is the question for cpt1c in cancer cells. Cell death & disease 21 36693836
2024 CPT1C-positive cancer-associated fibroblast facilitates immunosuppression through promoting IL-6-induced M2-like phenotype of macrophage. Oncoimmunology 19 38746869
2011 The CPT1C 5'UTR contains a repressing upstream open reading frame that is regulated by cellular energy availability and AMPK. PloS one 18 21961029
2023 CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis. Acta biochimica et biophysica Sinica 17 37078750
2018 Mechanisms of CPT1C-Dependent AMPAR Trafficking Enhancement. Frontiers in molecular neuroscience 17 30135643
2019 A novel CPT1C variant causes pure hereditary spastic paraplegia with benign clinical course. Annals of clinical and translational neurology 15 30911584
2024 APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition. Cell communication and signaling : CCS 10 38783346
2023 CPT1C is required for synaptic plasticity and oscillatory activity that supports motor, associative and non-associative learning. The Journal of physiology 10 37309891
2022 Mutant p53-microRNA-200c-ZEB2-Axis-Induced CPT1C Elevation Contributes to Metabolic Reprogramming and Tumor Progression in Basal-Like Breast Cancers. Frontiers in oncology 10 35936710
2024 The YY1-CPT1C signaling axis modulates the proliferation and metabolism of pancreatic tumor cells under hypoxia. Biochemical pharmacology 9 38996932
2023 Cpt1c Downregulation Causes Plasma Membrane Remodelling and Anthracycline Resistance in Breast Cancer. International journal of molecular sciences 9 36674468
2023 Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence. International journal of biological sciences 7 37151873
2025 CPT1C deficiency in SF1 neurons impairs early metabolic adaptation to dietary fats, leading to obesity. Molecular metabolism 4 40268191
2024 Expanding molecular and clinical spectrum of CPT1C-associated hereditary spastic paraplegia (SPG73)-a case series. Annals of clinical and translational neurology 2 39737739
2023 Proteomic analysis by 4D label-free MS-PRM identified that Nptx1, Ptpmt1, Slc25a11, and Cpt1c are involved in diabetes-associated cognitive dysfunction. The International journal of neuroscience 2 38099467
2019 Molecular characterization, genomic structure and expression analysis of a gene (CATL1/CPT1C) encoding a third member of the human carnitine acyltransferase family. Genomics 2 31128263
2026 Dual regulatory roles of CPT1C in chronic stress-induced depression-related outcomes. Molecular psychiatry 0 41741705
2026 Fenofibrate targets PPARα-CPT1C axis to reverse aging by regulating lipid metabolism and mitochondrial function. Pharmacological research 0 41765248

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