Affinage

CPT1A

Carnitine O-palmitoyltransferase 1, liver isoform · UniProt P50416

Length
773 aa
Mass
88.4 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CPT1A is the rate-limiting outer mitochondrial membrane enzyme that transfers long-chain acyl groups from coenzyme A to carnitine, generating acylcarnitines for import into the mitochondrial matrix and subsequent β-oxidation; this activity is allosterically inhibited by malonyl-CoA, with sensitivity modulated by mitochondrial morphology and antagonized by butyryl-CoA at Arg243 (PMID:31900483, PMID:36917141, PMID:34035164). Transcription of CPT1A is driven through distinct intronic elements by PPARα and PGC-1α and is epigenetically repressed by HDAC1 recruited via SP1 and HNF4α, while post-translationally CPT1A protein is stabilized by USP50-mediated deubiquitination and SIRT1-mediated deacetylation at Lys675 (PMID:20638986, PMID:31654770, PMID:34976224, PMID:37293270). Beyond its canonical metabolic role, CPT1A functions as a scaffolding and enzymatic hub: it recruits ZDHHC4 to palmitoylate MAVS for antiviral innate immune signaling, succinylates MFF and ATG16L1 to regulate mitochondrial fission and autophagy respectively, and anchors Bcl-2 at its BH3 domain to suppress the mitochondrial apoptotic pathway (PMID:38016475, PMID:39956875, PMID:37961047, PMID:34413485). Loss-of-function mutations in CPT1A cause CPT1A deficiency, a Mendelian disorder of impaired hepatic long-chain fatty acid oxidation (PMID:12189492).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    Defining the genomic architecture and establishing CPT1A as essential for human FAO: prior to this, CPT1A's full gene structure and disease-causing alleles were incompletely catalogued; mapping 20 exons across 60 kb and identifying six novel loss-of-function mutations in CPT1A-deficient patients confirmed CPT1A as indispensable for mitochondrial long-chain fatty acid import.

    Evidence Genomic mapping and sequencing of CPT1A exons/introns in deficiency patients with enzymatic validation in fibroblasts

    PMID:12189492

    Open questions at the time
    • Genotype–phenotype correlations for individual mutations not established
    • Residual enzymatic activity thresholds for disease not defined
  2. 2010 High

    Resolving how CPT1A transcription is coordinately induced during fasting: it was unclear whether PPARα and PGC-1α acted through the same cis-element; reporter and knockdown experiments showed they use distinct intronic elements (second intron for PPARα, first intron for PGC-1α), establishing independent transcriptional axes.

    Evidence Luciferase reporters with mutagenesis, PGC-1α shRNA, and in vivo fasted rat model

    PMID:20638986

    Open questions at the time
    • Identity of transcription factors mediating PGC-1α's effect through the first intron unknown
    • Chromatin context and enhancer looping not characterized
  3. 2018 High

    Two parallel advances refined CPT1A's regulatory and pharmacological landscape: (1) baicalin was identified as a direct allosteric CPT1A activator with isoform selectivity via chemoproteomics and binding-site mutagenesis; (2) T cell-specific Cpt1a knockout showed that long-chain FAO through CPT1A is largely dispensable for effector, memory, and regulatory T cell formation, challenging prior pharmacological conclusions based on etomoxir.

    Evidence Chemoproteomics with binding-site mutagenesis and in vivo metabolic readouts (baicalin); conditional T cell Cpt1a KO with differentiation and metabolic assays (T cell dispensability)

    PMID:29891721 PMID:30043753

    Open questions at the time
    • Structural basis of baicalin's allosteric activation unresolved
    • Cell types where CPT1A-dependent FAO is truly essential versus dispensable remain context-dependent
  4. 2018 High

    Identifying a non-metabolic trafficking role: CPT1A was found to interact with Rab14, facilitating fatty acid transfer from lipid droplets to mitochondria, thereby linking CPT1A to intracellular lipid trafficking beyond its catalytic function at the outer mitochondrial membrane.

    Evidence LC-MS/MS interactome, Co-IP, proximity ligation assay, BODIPY-C16 pulse-chase in nasopharyngeal carcinoma cells

    PMID:29721083

    Open questions at the time
    • Direct versus indirect nature of CPT1A–Rab14 interaction not fully resolved
    • Whether Rab14 interaction requires CPT1A enzymatic activity unknown
  5. 2019 High

    Uncovering epigenetic repression of CPT1A: ethanol was shown to recruit HDAC1 to the CPT1A promoter via SP1 (proximal) and HNF4α (distal), causing H3K9 deacetylation and transcriptional silencing, which butyrate reverses by inhibiting HDAC1 and enabling p300-HAT binding.

    Evidence ChIP for HDAC1, SP1, HNF4α, p300, and H3K9ac at CPT1A promoter in ethanol-fed mice and primary hepatocytes

    PMID:31654770

    Open questions at the time
    • Whether other HDACs contribute to CPT1A silencing not tested
    • Genome-wide effects of ethanol on FAO gene promoters not assessed
  6. 2020 Medium

    Establishing CPT1A-dependent FAO as a driver of oncogenic Wnt signaling: CPT1A activity in adipocyte-exposed colon cancer cells was shown to promote acetylation and nuclear translocation of β-catenin, linking FAO-derived acetyl-CoA to epigenetic and transcriptional reprogramming.

    Evidence CPT1A knockdown, β-catenin acetylation assay, nuclear fractionation, xenograft model

    PMID:32913185

    Open questions at the time
    • The acetyltransferase responsible for β-catenin acetylation downstream of CPT1A not identified
    • Whether this mechanism operates beyond adipocyte-exposed contexts is unclear
  7. 2021 High

    Two findings expanded CPT1A's role to anti-apoptotic signaling and tissue protection: CPT1A was shown to directly anchor Bcl-2 via its BH3 domain to prevent cytochrome C release in macrophages, and conditional CPT1A overexpression in renal tubular cells restored FAO and protected against kidney fibrosis in three independent models.

    Evidence Co-IP with BH3 domain mapping and activity-dependence in IPF lung tissue (apoptosis); conditional knock-in transgenic mouse with UUO, folic acid, and adenine fibrosis models (renal protection)

    PMID:33465052 PMID:34413485

    Open questions at the time
    • Whether CPT1A–Bcl-2 interaction is regulated by metabolic state unknown
    • Structural basis of the BH3-domain interaction not resolved
  8. 2021 High

    Butyryl-CoA was identified as an endogenous antagonist of malonyl-CoA inhibition at CPT1A Arg243, linking gut-derived butyrate metabolism through ACSS2 to CPT1A activation and iTreg differentiation.

    Evidence CPT1A Arg243 mutagenesis, ACSS2 inhibitor, metabolic and T cell differentiation assays, mouse colitis model

    PMID:34035164

    Open questions at the time
    • Whether other short-chain acyl-CoAs compete at Arg243 not tested
    • Structural mechanism of butyryl-CoA antagonism not determined
  9. 2022 High

    Post-translational stabilization of CPT1A was defined: mitochondrial STAT3 induces USP50 via NF-κB, and USP50 deubiquitinates CPT1A to prevent its proteasomal degradation, establishing a signaling axis that stabilizes CPT1A during sepsis-driven metabolic reprogramming in macrophages.

    Evidence Co-IP (CPT1A–USP50), ChIP (NF-κB at USP50 promoter), USP50 knockdown, knock-in mouse model

    PMID:34976224

    Open questions at the time
    • Specific ubiquitin linkage type and E3 ligase targeting CPT1A for degradation not identified
    • Whether USP50 regulation of CPT1A operates outside macrophages unknown
  10. 2022 Medium

    CPT1A's role was extended to mitophagy regulation: CPT1A directly binds PHB2 and modulates the PHB2–PARL interaction to promote PINK1–Parkin-dependent mitophagy, with increased CPT1A activity (via M593S gain-of-function mutation) enhancing this process in cardiac endothelial cells.

    Evidence Co-IP, CPT1A M593S mutagenesis, adenoviral overexpression, db/db diabetic mouse model

    PMID:37042471

    Open questions at the time
    • Whether CPT1A enzymatic activity or scaffolding is the critical determinant for PHB2 binding not separated
    • Confirmation in non-cardiac cell types lacking
  11. 2022 Medium

    CPT1A-dependent FAO was shown to provide carbon precursors for nucleotide biosynthesis: 13C-palmitate tracing demonstrated that CPT1A knockdown reduces palmitate-derived carbons incorporated into pyrimidines, directly linking FAO to proliferative capacity.

    Evidence 13C-palmitate isotopomer tracing, nucleoside metabolite profiling, CPT1A knockdown in nasopharyngeal carcinoma

    PMID:35411000

    Open questions at the time
    • Quantitative contribution of FAO versus other carbon sources to nucleotide pools not determined
    • Single cancer type studied
  12. 2023 High

    Mitochondrial morphology was established as a biophysical regulator of CPT1A: fragmentation reduces malonyl-CoA sensitivity (increasing FAO) while elongation increases it, revealing that the physical state of the outer mitochondrial membrane tunes CPT1A allosteric regulation.

    Evidence MFN2/DRP1 genetic manipulation, 13C metabolic tracing, CPT1 malonyl-CoA sensitivity assays in multiple cell types

    PMID:36917141

    Open questions at the time
    • Biophysical mechanism by which membrane curvature alters malonyl-CoA binding not defined
    • Whether this applies to CPT1B and CPT1C isoforms unknown
  13. 2023 Medium

    A novel non-canonical enzymatic activity was attributed to CPT1A — lysine succinyltransferase (LSTase) activity: CPT1A succinylates MFF to promote mitochondria-associated membrane formation and SREBP1 activation, and succinylates ATG16L1 to drive autophagosome formation, revealing CPT1A as an acyltransferase with substrates beyond carnitine.

    Evidence Succinylation assays, LSTase activity assays, Co-IP (CPT1A–MFF, CPT1A–ATG16L1), autophagy flux assays, tumor models

    PMID:37961047 PMID:39956875

    Open questions at the time
    • LSTase activity demonstrated by single lab; independent replication needed
    • Catalytic residues responsible for succinyltransferase activity not identified
    • Substrate scope of this activity unknown
  14. 2023 High

    CPT1A was shown to function as a scaffolding hub for innate antiviral immunity: CPT1A recruits the ER palmitoyltransferase ZDHHC4 to palmitoylate MAVS at Cys79, shifting ubiquitination from K48-linked (degradative) to K63-linked (activating) and sustaining type I interferon responses.

    Evidence Co-IP, palmitoylation and ubiquitination linkage assays, genetic CPT1A manipulation, IFN-I reporter assays

    PMID:38016475

    Open questions at the time
    • Whether CPT1A enzymatic (acyltransfer) activity is required for ZDHHC4 recruitment not separated from scaffolding
    • How CPT1A on the outer mitochondrial membrane contacts ER-localized ZDHHC4 mechanistically unclear
  15. 2023 Medium

    SIRT1 was identified as a deacetylase stabilizing CPT1A: SIRT1 deacetylates Lys675, suppressing ubiquitin-dependent degradation, defining a second post-translational stabilization axis complementary to USP50-mediated deubiquitination.

    Evidence Co-IP, site-directed mutagenesis (K675), acetylation/deacetylation assays, SIRT1 overexpression/knockdown in HepG2

    PMID:37293270

    Open questions at the time
    • The E3 ligase that ubiquitinates acetylated CPT1A not identified
    • Whether Lys675 acetylation and USP50-mediated deubiquitination converge on the same degradation pathway unknown
  16. 2023 Medium

    CPT1A mRNA stability was shown to be regulated by m6A-dependent mechanisms involving IGF2BP1, which recognizes m6A marks on CPT1A mRNA to enhance its stability; IGF2BP1 is itself stabilized by USP10 or activated by RNF5-mediated K63 ubiquitination.

    Evidence MeRIP-seq, RNA pulldown, Co-IP, deubiquitination/ubiquitination assays, mRNA stability assays in breast cancer and hepatocellular carcinoma

    PMID:36632454 PMID:39734009

    Open questions at the time
    • Specific m6A sites on CPT1A mRNA functionally validated by mutagenesis not yet reported
    • Whether m6A regulation of CPT1A mRNA operates in non-cancer contexts unknown
  17. 2024 High

    CPT1A loss was linked to epigenetic and metabolic rewiring in hepatocellular carcinoma: Cpt1a ablation reduces acetyl-CoA, decreasing histone acetylation and repressing BCAA catabolism genes, causing BCAA accumulation and mTOR hyperactivation — creating a therapeutically exploitable vulnerability.

    Evidence Genetic Cpt1a ablation, histone acetylation and metabolomics assays, mTOR signaling, xenograft and de novo liver tumor models with mTOR inhibitor rescue

    PMID:38823763

    Open questions at the time
    • Whether CPT1A-derived acetyl-CoA specifically acetylates histones at BCAA gene loci versus globally not resolved
    • Generalizability to non-TP53-mutant contexts untested
  18. 2024 High

    CPT1A was found to restrain c-Myc ubiquitination and degradation, forming a positive feedback loop (c-Myc transcriptionally activates CPT1A) that activates the NRF2/GPX4 antioxidant system and suppresses ferroptosis in lung cancer stem cells.

    Evidence Lung epithelial-specific Cpt1a KO mouse, ChIP (c-Myc on CPT1A promoter), ubiquitination assays, ferroptosis assays, metabolomics/transcriptomics

    PMID:38453925

    Open questions at the time
    • Mechanism by which CPT1A inhibits c-Myc ubiquitination (direct interaction versus metabolic effect) not distinguished
    • Whether this loop operates in non-stem cancer cells unknown
  19. 2024 Medium

    CPT1 inhibition was shown to stimulate cardiomyocyte proliferation via reduced PARP1-mediated ADP-ribosylation of DUSP1, decreasing p38 MAPK phosphorylation, revealing a metabolic brake on cardiac regeneration.

    Evidence Cardiac-specific Cpt1a/Cpt1b double KO mice, etomoxir, ADP-ribosylation and p38 assays, cardiac function post-MI

    PMID:40041918

    Open questions at the time
    • CPT1A versus CPT1B individual contributions not separated (double KO used)
    • How FAO inhibition decreases PARP1 expression mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain: the structural basis of CPT1A's allosteric regulation by malonyl-CoA and membrane curvature; whether the newly reported succinyltransferase (LSTase) activity is an intrinsic catalytic function or requires cofactors; the identity of the E3 ligase(s) targeting CPT1A for ubiquitin-dependent degradation; and how CPT1A scaffolding at the outer mitochondrial membrane coordinates with ER-resident partners (ZDHHC4) at membrane contact sites.
  • No high-resolution structure of full-length CPT1A with malonyl-CoA
  • LSTase activity awaits independent replication and catalytic-residue identification
  • E3 ligase(s) mediating CPT1A ubiquitination unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005739 mitochondrion 6
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 2
Partners
ATG16L1BCL2MAVSPHB2RAB14USP50VDAC1ZDHHC4

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 CPT1A catalyzes the rate-limiting step of mitochondrial fatty acid oxidation by converting long-chain acyl-CoA into acyl-carnitines, enabling their transport across the inner mitochondrial membrane; this activity is inhibited by malonyl-CoA. Review synthesizing enzymatic assays, genetic models, and metabolic studies Endocrinology High 31900483
2023 Mitochondrial fragmentation reduces malonyl-CoA inhibition of CPT1A (increasing FAO), while mitochondrial elongation increases CPT1A sensitivity to malonyl-CoA inhibition, establishing mitochondrial morphology as a regulator of CPT1A activity and long-chain fatty acid utilization. Genetic manipulation of MFN2 and DRP1, respirometry, metabolic tracing (13C), CPT1 malonyl-CoA sensitivity assays The EMBO journal High 36917141
2021 Butyrate is converted by ACSS2 to butyryl-CoA (BCoA), which antagonizes malonyl-CoA binding at Arg243 of CPT1A, thereby relieving malonyl-CoA inhibition, increasing CPT1A activity, promoting fatty acid oxidation, and facilitating iTreg differentiation. CPT1A mutagenesis (Arg243), ACSS2 inhibitor, metabolic assays, T cell differentiation assays, mouse colitis model Proceedings of the National Academy of Sciences of the United States of America High 34035164
2018 Baicalin directly activates hepatic CPT1A with isoform selectivity through allosteric binding; disruption of the predicted binding site abolished the beneficial anti-steatosis effects of baicalin. Quantitative chemoproteomic profiling, binding-site mutagenesis, in vivo metabolic assays in diet-induced obesity mouse model Proceedings of the National Academy of Sciences of the United States of America High 29891721
2023 CPT1A recruits the ER-localized palmitoyltransferase ZDHHC4 to catalyze palmitoylation of MAVS at Cys79, which promotes MAVS stabilization and activation by inhibiting K48-linked and facilitating K63-linked ubiquitination, thereby sustaining type I interferon responses. Co-immunoprecipitation, palmitoylation assays, ubiquitination assays (K48/K63 linkage), genetic CPT1A manipulation, IFN-I reporter assays Molecular cell High 38016475
2022 Mitochondrial STAT3 prevents CPT1A ubiquitination and degradation in macrophages through induction of the deubiquitinase USP50 (via NF-κB binding the USP50 promoter), thereby stabilizing CPT1A protein and promoting fatty acid oxidation during sepsis. Mass spectrometry, Co-immunoprecipitation (CPT1A-USP50), ChIP assay (NF-κB at USP50 promoter), USP50 knockdown, metabolic assays, knock-in mouse model Theranostics High 34976224
2021 CPT1A directly interacts with Bcl-2 at its BH3 domain in mitochondria, anchoring Bcl-2 to prevent cytochrome C release and apoptosis; this interaction is dependent on CPT1A enzymatic activity and is present in lung macrophages from IPF patients. Co-immunoprecipitation, domain-mapping (BH3 domain), CPT1A activity inhibition, patient tissue analysis, bleomycin mouse model Cell death and differentiation High 34413485
2023 CPT1A promotes succinylation of mitochondrial fission factor (MFF) through its lysine succinyltransferase (LSTase) activity, which promotes mitochondria-associated membrane formation and SREBP1 activation, enhancing lipid desaturation and stemness in ovarian cancer stem cells. Succinylation assays, LSTase activity assays, CPT1A inhibition (Glyburide), Co-IP, in vitro and in vivo tumor models Communications biology Medium 39956875
2023 SIRT1 deacetylates CPT1A at Lys675, suppressing its ubiquitin-dependent degradation, thereby stabilizing CPT1A protein and promoting fatty acid oxidation in hepatocytes. Co-immunoprecipitation, acetylation/deacetylation assays, site-directed mutagenesis (Lys675), SIRT1 overexpression/knockdown, CPT1A activity assays in HepG2 cells Gastroenterology report Medium 37293270
2022 CPT1A modulates the PHB2-PARL interaction by directly binding to PHB2; increased CPT1A activity (via L-carnitine or M593S mutation) enhances the PHB2-PARL interaction, promoting PINK1-Parkin-dependent mitophagy and improving mitochondrial function in cardiac endothelial cells. Co-immunoprecipitation, Western blotting, CPT1A activity assays with mutation (M593S), adenoviral overexpression, db/db mouse model Acta physiologica (Oxford, England) Medium 37042471
2023 CPT1A covalently binds to Cys96 of its own protein when bound by the inhibitor DHP-B, which blocks FAO and disrupts the mitochondrial CPT1A-VDAC1 protein interaction, increasing mitochondrial permeability in colorectal cancer cells. Covalent binding assays, Co-immunoprecipitation (CPT1A-VDAC1), mitochondrial permeability assays, in vitro and in vivo tumor models Redox biology Medium 37977042
2023 T cell-derived IFN-γ induces CPT1A expression and fatty acid oxidation in cancer cells through an AMPK-dependent mechanism, conferring resistance to cytotoxic T lymphocyte killing; CPT1A repression abrogates prosurvival signaling under immune cytolytic stress. CPT1A knockdown/overexpression, IFN-γ stimulation, AMPK inhibition, CTL cytotoxicity assays, Seahorse metabolic analysis, in vivo tumor models with CAR-T cells Proceedings of the National Academy of Sciences of the United States of America High 37722058
2020 CPT1A-dependent FAO promotes acetylation and nuclear translocation of β-catenin in colon cancer cells exposed to adipocytes; silencing CPT1A abolished β-catenin nuclear translocation and Wnt/β-catenin target gene expression. CPT1A knockdown, β-catenin acetylation assay, nuclear fractionation, Wnt target gene expression, xenograft tumor model Cell death & disease Medium 32913185
2024 CPT1A restrains ubiquitination and degradation of c-Myc, while c-Myc transcriptionally activates CPT1A expression, forming a positive feedback loop that activates the NRF2/GPX4 antioxidant system and reduces ACSL4 expression to suppress ferroptosis in lung cancer stem cells. Lung epithelial-specific Cpt1a-knockout mouse model, metabolomics, transcriptomics, ubiquitination assays, ChIP assay (c-Myc on CPT1A promoter), ferroptosis assays Signal transduction and targeted therapy High 38453925
2024 CPT1A loss in TP53-mutant hepatocellular carcinoma reduces acetyl-CoA production, which decreases histone acetylation and epigenetically represses BCAA catabolism, leading to BCAA accumulation and mTOR hyperactivation, creating sensitivity to mTOR inhibition. Genetic Cpt1a ablation, histone acetylation assays, metabolomics (acetyl-CoA, BCAA), mTOR signaling assays, xenograft and de novo liver tumor models, mTOR inhibitor treatment Cancer letters High 38823763
2010 PPARα and PGC-1α stimulate CPT1A transcription through distinct gene elements: PPARα acts through a binding site in the second intron, while PGC-1α acts through sequences in the first intron; PGC-1α knockdown does not abolish CPT1A induction by the PPARα ligand WY14643. PPARα binding site identification, luciferase reporter assays, PGC-1α shRNA knockdown, fasted rat in vivo model with luciferase vectors, WY14643 treatment Molecular and cellular endocrinology High 20638986
2019 Ethanol induces CPT1A promoter histone H3K9 deacetylation via HDAC1 recruitment mediated by SP1 (proximal region) and HNF4α (distal region), causing transcriptional repression; butyrate inhibits HDAC1 and enables p300-HAT binding to rescue CPT1A expression. Chromatin immunoprecipitation (ChIP) for HDAC1, SP1, HNF4α, p300 at CPT1A promoter; in vivo ethanol-fed mouse model; in vitro primary hepatocyte treatment Cellular and molecular gastroenterology and hepatology High 31654770
2018 CPT1A interacts with Rab14, and this interaction facilitates trafficking of fatty acids from lipid droplets to mitochondria, decreasing radiation-induced lipid accumulation and maximizing ATP production to confer radiation resistance in nasopharyngeal carcinoma cells. LC-MS/MS interactome, Co-immunoprecipitation, immunofluorescence, proximity ligation assay, computational protein-protein interaction prediction, pulse-chase fatty acid trafficking assay (BODIPY C16/MitoTracker), Rab14 knockdown Theranostics High 29721083
2024 CPT1A not only promotes FAO but also anchors Bcl-2 to the mitochondrial membrane in podocytes, preventing cytochrome C release and inhibiting the mitochondrial apoptotic pathway; a transcription factor FOXA1 was identified as a novel transcriptional regulator of CPT1A. CPT1A overexpression in streptozotocin-diabetic mice, Co-immunoprecipitation (CPT1A-Bcl2), cytochrome C release assays, FOXA1 ChIP/reporter assays, albuminuria and glomerulosclerosis readouts Diabetes Medium 38506804
2024 CPT1 inhibition (cardiac-specific Cpt1a/Cpt1b knockout or etomoxir) decreases PARP1 expression and reduces ADP-ribosylation of DUSP1, leading to decreased p38 MAPK phosphorylation and stimulation of cardiomyocyte proliferation and cardiac regeneration post-myocardial infarction. Cardiac-specific Cpt1a/Cpt1b knockout mice, etomoxir pharmacology, ADP-ribosylation assays of DUSP1, p38 MAPK phosphorylation assays, cardiomyocyte proliferation and cardiac function readouts Acta pharmaceutica Sinica. B Medium 40041918
2022 CPT1A-mediated FAO promotes cell proliferation in nasopharyngeal carcinoma by generating acetyl equivalents and carbon precursors for nucleotide biosynthesis; 13C-palmitate tracing shows CPT1A knockdown reduces palmitate-derived carbons incorporated into pyrimidines. 13C-palmitate isotopomer tracing, Seahorse XF analysis, CPT1A knockdown, nucleoside metabolite profiling, xenograft model Cell death & disease Medium 35411000
2021 CPT1A overexpression in renal tubular epithelial cells restores oxidative phosphorylation, increases palmitate oxidation and ATP levels, and reduces fibrotic marker expression; this gain-of-function protected against three models of renal fibrosis in conditional transgenic mice. Conditional CPT1A knock-in transgenic mouse, three fibrosis models (UUO, folic acid nephropathy, adenine), palmitate oxidation assays, ATP measurement, fibrosis scoring, AAV-mediated post-injury delivery The Journal of clinical investigation High 33465052
2022 Neutrophil chemotaxis and trafficking to sites of infection requires Cpt1a-dependent mitochondrial fatty acid oxidation for amplification of chemoattractant signals; pharmacologic Cpt1a inhibition impairs neutrophil trafficking and increases mortality in bacterial pneumonia. Pharmacological CPT1A inhibition in mouse pneumonia model, human phenome association study with CPT1A variant rs2229738_T, neutrophil chemotaxis assays, in vivo infection mortality studies Communications biology Medium 36513703
2024 RNF5 promotes K63-type ubiquitination of IGF2BP1, which enhances CPT1A mRNA stabilization through m6A modification, thereby increasing CPT1A protein levels and fatty acid oxidation in steatotic hepatocellular carcinoma. Protein interaction assays, ubiquitination assays (K63 linkage), m6A modification (MeRIP), CPT1A mRNA stability assays, lipidomics, transcriptomics Cancer letters Medium 39734009
2023 IGF2BP1 directly recognizes and binds m6A sites on CPT1A mRNA and enhances its stability, with IGF2BP1 being stabilized by deubiquitinase USP10 that binds, deubiquitinates, and increases IGF2BP1 levels, ultimately mediating CPT1A-dependent breast cancer metastasis. MeRIP-seq, Co-IP, RNA pulldown, USP10 deubiquitination assay, CPT1A mRNA stability assays, in vitro and in vivo metastasis models International journal of biological sciences Medium 36632454
2023 CPT1A interacts with the autophagy-related protein ATG16L1 and stimulates succinylation of ATG16L1, which drives autophagosome formation and autophagy, conferring chemoresistance in hypopharyngeal squamous cell carcinoma. Co-immunoprecipitation (CPT1A-ATG16L1), succinylation assays, autophagy flux assays, CPT1A inhibition, cisplatin sensitivity assays in vitro and in vivo Cell insight Medium 37961047
2002 The human CPT1A gene spans 60 kb with 20 exons, has two alternate promoters, and numerous transcription factor-binding sites in the 5' upstream region; six novel loss-of-function mutations in CPT1A-deficient patients establish CPT1A as essential for mitochondrial long-chain fatty acid import and FAO in humans. Gene organization mapping using draft genome data, mutation identification by sequencing of exons/introns in CPT1A-deficient patients, CPT1 enzymatic activity in fibroblasts Human genetics High 12189492
2018 Using T cell-specific Cpt1a knockout mice, long-chain fatty acid oxidation via the ACC2/Cpt1a axis is shown to be largely dispensable for effector, memory, and regulatory T cell formation; etomoxir effects on T cells are independent of Cpt1a expression. T cell-specific Cpt1a conditional knockout mice, T cell differentiation assays, memory and regulatory T cell functional assays, metabolic analysis Cell metabolism High 30043753
2024 PACS2 positively regulates CPT1A expression in cardiomyocytes; silencing PACS2 downregulates CPT1A and upregulates DHODH, reversing high-glucose/palmitic-acid-induced ferroptosis, while CPT1A agonism in PACS2-silenced cells re-exacerbates ferroptosis and mitochondrial damage. PACS2 siRNA knockdown, CPT1A agonist, ferroptosis assays (iron, lipid peroxides, ROS), STZ/HFD mouse model, cardiac function and mitochondrial morphology analysis Cardiovascular diabetology Medium 39633391

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 CPT1A-mediated Fat Oxidation, Mechanisms, and Therapeutic Potential. Endocrinology 551 31900483
2018 Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation. Cell metabolism 327 30043753
2018 CPT1A-mediated fatty acid oxidation promotes colorectal cancer cell metastasis by inhibiting anoikis. Oncogene 300 29995871
2021 Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis. The Journal of clinical investigation 277 33465052
2018 Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis. Proceedings of the National Academy of Sciences of the United States of America 276 29891721
2014 Lipid catabolism via CPT1 as a therapeutic target for prostate cancer. Molecular cancer therapeutics 257 25122071
2018 Targeting CPT1A-mediated fatty acid oxidation sensitizes nasopharyngeal carcinoma to radiation therapy. Theranostics 224 29721083
2015 Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. Blood 185 26276667
2010 Peroxisome proliferator activated receptor alpha (PPARalpha) and PPAR gamma coactivator (PGC-1alpha) induce carnitine palmitoyltransferase IA (CPT-1A) via independent gene elements. Molecular and cellular endocrinology 172 20638986
2024 Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer. Signal transduction and targeted therapy 149 38453925
2023 Mitochondrial morphology controls fatty acid utilization by changing CPT1 sensitivity to malonyl-CoA. The EMBO journal 145 36917141
2021 Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation. Proceedings of the National Academy of Sciences of the United States of America 141 34035164
2022 Mitochondrial STAT3 exacerbates LPS-induced sepsis by driving CPT1a-mediated fatty acid oxidation. Theranostics 123 34976224
2023 Mitochondrial CPT1A: Insights into structure, function, and basis for drug development. Frontiers in pharmacology 109 37033619
2022 CPT1A-mediated fatty acid oxidation promotes cell proliferation via nucleoside metabolism in nasopharyngeal carcinoma. Cell death & disease 99 35411000
2021 iRGD-modified exosomes effectively deliver CPT1A siRNA to colon cancer cells, reversing oxaliplatin resistance by regulating fatty acid oxidation. Molecular oncology 85 34213835
2020 Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 82 32666604
2012 Increased mitochondrial activity in BMP7-treated brown adipocytes, due to increased CPT1- and CD36-mediated fatty acid uptake. Antioxidants & redox signaling 81 22938691
1987 Mutants of Saccharomyces cerevisiae defective in sn-1,2-diacylglycerol cholinephosphotransferase. Isolation, characterization, and cloning of the CPT1 gene. The Journal of biological chemistry 80 3029130
2022 The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα. Cell communication and signaling : CCS 79 35392915
2024 ACACA reduces lipid accumulation through dual regulation of lipid metabolism and mitochondrial function via AMPK- PPARα- CPT1A axis. Journal of translational medicine 78 38395901
2016 High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia. EBioMedicine 77 27916548
2023 CPT1A-mediated fatty acid oxidation confers cancer cell resistance to immune-mediated cytolytic killing. Proceedings of the National Academy of Sciences of the United States of America 75 37722058
2021 Targeted Inhibition of LPL/FABP4/CPT1 fatty acid metabolic axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer. International journal of biological sciences 70 34803493
2020 Upregulation of CPT1A is essential for the tumor-promoting effect of adipocytes in colon cancer. Cell death & disease 67 32913185
2023 Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner. International journal of biological sciences 66 36632454
2015 High fructose consumption induces DNA methylation at PPARα and CPT1A promoter regions in the rat liver. Biochemical and biophysical research communications 63 26519879
2014 Methylation at CPT1A locus is associated with lipoprotein subfraction profiles. Journal of lipid research 63 24711635
2020 Carbohydrate and fat intake associated with risk of metabolic diseases through epigenetics of CPT1A. The American journal of clinical nutrition 59 32930325
2022 CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis. Redox biology 58 36427397
2023 CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunity. Molecular cell 51 38016475
2021 Multiomic analysis identifies CPT1A as a potential therapeutic target in platinum-refractory, high-grade serous ovarian cancer. Cell reports. Medicine 50 35028612
2011 The effect of clozapine on the AMPK-ACC-CPT1 pathway in the rat frontal cortex. The international journal of neuropsychopharmacology 49 21733226
2021 A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis. Journal of nanobiotechnology 48 34789275
2018 CPT1 regulates the proliferation of pulmonary artery smooth muscle cells through the AMPK-p53-p21 pathway in pulmonary arterial hypertension. Molecular and cellular biochemistry 48 30511343
2018 Epigenetic regulation of carnitine palmitoyltransferase 1 (Cpt1a) by high fat diet. Biochimica et biophysica acta. Gene regulatory mechanisms 47 30605728
2023 L-carnitine alleviates cardiac microvascular dysfunction in diabetic cardiomyopathy by enhancing PINK1-Parkin-dependent mitophagy through the CPT1a-PHB2-PARL pathways. Acta physiologica (Oxford, England) 44 37042471
2014 Targeting prostate cancer cell metabolism: impact of hexokinase and CPT-1 enzymes. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 44 25501281
2021 Fatty acid β-oxidation promotes breast cancer stemness and metastasis via the miRNA-328-3p-CPT1A pathway. Cancer gene therapy 43 34045663
2022 Inhibition of Cpt1a alleviates oxidative stress-induced chondrocyte senescence via regulating mitochondrial dysfunction and activating mitophagy. Mechanisms of ageing and development 42 35728631
2019 Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury. Cellular and molecular gastroenterology and hepatology 42 31654770
2022 Rhein Improves Renal Fibrosis by Restoring Cpt1a-Mediated Fatty Acid Oxidation through SirT1/STAT3/twist1 Pathway. Molecules (Basel, Switzerland) 41 35408745
2021 Targeting Cpt1a-Bcl-2 interaction modulates apoptosis resistance and fibrotic remodeling. Cell death and differentiation 40 34413485
2005 Positive regulation of hepatic carnitine palmitoyl transferase 1A (CPT1A) activities by soy isoflavones and L-carnitine. European journal of nutrition 40 16362726
2022 Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC. Acta biochimica et biophysica Sinica 36 35130611
2021 Simultaneously targeting SOAT1 and CPT1A ameliorates hepatocellular carcinoma by disrupting lipid homeostasis. Cell death discovery 36 34052835
2020 CPT1A Over-Expression Increases Reactive Oxygen Species in the Mitochondria and Promotes Antioxidant Defenses in Prostate Cancer. Cancers 36 33218188
2002 Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia. Human genetics 36 12189492
2017 CPT1A Missense Mutation Associated With Fatty Acid Metabolism and Reduced Height in Greenlanders. Circulation. Cardiovascular genetics 35 28611031
2021 Differential contributions of choline phosphotransferases CPT1 and CEPT1 to the biosynthesis of choline phospholipids. Journal of lipid research 32 34331935
2024 CPT1A-IL-10-mediated macrophage metabolic and phenotypic alterations ameliorate acute lung injury. Clinical and translational medicine 30 39090662
2024 PACS2/CPT1A/DHODH signaling promotes cardiomyocyte ferroptosis in diabetic cardiomyopathy. Cardiovascular diabetology 29 39633391
1984 Vibrio cholerae bacteriophage CP-T1: characterization of bacteriophage DNA and restriction analysis. Journal of virology 28 6328035
2024 CPT1A loss disrupts BCAA metabolism to confer therapeutic vulnerability in TP53-mutated liver cancer. Cancer letters 27 38823763
2023 A novel CPT1A covalent inhibitor modulates fatty acid oxidation and CPT1A-VDAC1 axis with therapeutic potential for colorectal cancer. Redox biology 27 37977042
2022 The lncRNA MIAT regulates CPT-1a mediated cardiac hypertrophy through m6A RNA methylation reading protein Ythdf2. Cell death discovery 26 35383152
2022 An integrated network pharmacology and cell metabolomics approach to reveal the role of rhein, a novel PPARα agonist, against renal fibrosis by activating the PPARα-CPT1A axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 26 35567992
2006 Variants within the muscle and liver isoforms of the carnitine palmitoyltransferase I (CPT1) gene interact with fat intake to modulate indices of obesity in French-Canadians. Journal of molecular medicine (Berlin, Germany) 26 17089095
2024 ASS1 enhances anoikis resistance via AMPK/CPT1A-mediated fatty acid metabolism in ovarian cancer. Cancer letters 25 38914306
2022 l-Carnitine therapy improves right heart dysfunction through Cpt1-dependent fatty acid oxidation. Pulmonary circulation 25 35911183
2012 Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart. Mechanisms of ageing and development 25 22322067
2022 The role of CPT1A as a biomarker of breast cancer progression: a bioinformatic approach. Scientific reports 24 36180554
2024 The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7. Cardiovascular diabetology 23 38195542
2022 Neutrophil trafficking to the site of infection requires Cpt1a-dependent fatty acid β-oxidation. Communications biology 23 36513703
2019 The PPARδ Agonist GW501516 Improves Lipolytic/Lipogenic Balance through CPT1 and PEPCK during the Development of Pre-Implantation Bovine Embryos. International journal of molecular sciences 23 31810173
2017 Association of CYP2C9, CYP2A6, ACSM2A, and CPT1A gene polymorphisms with adverse effects of valproic acid in Chinese patients with epilepsy. Epilepsy research 23 28315807
2013 Effects of cannabinoid receptor 1 (brain) on lipid accumulation by transcriptional control of CPT1A and CPT1B. Animal genetics 22 23914904
2023 CPT1A modulates PI3K/Akt/mTOR pathway to promote preeclampsia. Placenta 21 36702079
2019 CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis. Scientific reports 21 31527712
2023 Berberine alleviates non-alcoholic hepatic steatosis partially by promoting SIRT1 deacetylation of CPT1A in mice. Gastroenterology report 20 37293270
2022 Vitamin D Counteracts Lipid Accumulation, Augments Free Fatty Acid-Induced ABCA1 and CPT-1A Expression While Reducing CD36 and C/EBPβ Protein Levels in Monocyte-Derived Macrophages. Biomedicines 20 35453525
2020 LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells. Molecules (Basel, Switzerland) 20 32916992
2010 Aerobic exercise's reversal of insulin resistance by activating AMPKα-ACC-CPT1 signaling in the skeletal muscle of C57BL/6 mice. International journal of sport nutrition and exercise metabolism 20 20975105
2025 CPT1A-mediated MFF succinylation promotes stemness maintenance in ovarian cancer stem cells. Communications biology 19 39956875
2022 Quercetin: a silent retarder of fatty acid oxidation in breast cancer metastasis through steering of mitochondrial CPT1. Breast cancer (Tokyo, Japan) 19 35511410
2022 Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres. Journal of neuro-oncology 19 36396930
2021 Carnitine palmitoyltransferase 1 (CPT1) alleviates oxidative stress and apoptosis of hippocampal neuron in response to beta-Amyloid peptide fragment Aβ25-35. Bioengineered 19 34424821
2012 Variants in CPT1A, FADS1, and FADS2 are Associated with Higher Levels of Estimated Plasma and Erythrocyte Delta-5 Desaturases in Alaskan Eskimos. Frontiers in genetics 19 22701466
2023 Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer's disease at CPT1A locus. Clinical epigenetics 18 37891690
2020 Terpenoids from Resina Commiphora Regulating Lipid Metabolism via Activating PPARα and CPT1 Expression. Organic letters 18 32301324
1985 Bacteriophage CP-T1 of Vibrio cholerae. Identification of the cell surface receptor. European journal of biochemistry 18 4065151
2024 Tubular CPT1A deletion minimally affects aging and chronic kidney injury. JCI insight 17 38516886
2023 Restoration of CPT1A-mediated fatty acid oxidation in mesothelial cells protects against peritoneal fibrosis. Theranostics 17 37649600
2016 Targeting CPT1A enhances metabolic therapy in human melanoma cells with the BRAF V600E mutation. The international journal of biochemistry & cell biology 17 27793752
2024 CPT1A Protects Podocytes From Lipotoxicity and Apoptosis In Vitro and Alleviates Diabetic Nephropathy In Vivo. Diabetes 16 38506804
2024 Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation. Acta pharmaceutica Sinica. B 16 40041918
2023 Gastric cancer cell-originated small extracellular vesicle induces metabolic reprogramming of BM-MSCs through ERK-PPARγ-CPT1A signaling to potentiate lymphatic metastasis. Cancer cell international 16 37158903
2023 CPT1A mediates chemoresistance in human hypopharyngeal squamous cell carcinoma via ATG16L1-dependent cellular autophagy. Cell insight 16 37961047
2023 Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN. International journal of molecular sciences 16 38003694
2023 FDXR drives primary and endocrine-resistant tumor cell growth in ER+ breast cancer via CPT1A-mediated fatty acid oxidation. Frontiers in oncology 15 37207154
2022 WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC. Lipids in health and disease 15 36384580
2022 Atorvastatin ameliorates lipid overload-induced mitochondrial dysfunction and myocardial hypertrophy by decreasing fatty acid oxidation through inactivation of the p-STAT3/CPT1 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 36402030
2021 Exogenous L-carnitine ameliorates burn-induced cellular and mitochondrial injury of hepatocytes by restoring CPT1 activity. Nutrition & metabolism 15 34167568
2020 Antiobesity and anti-inflammation effects of Hakka stir-fried tea of different storage years on high-fat diet-induced obese mice model via activating the AMPK/ACC/CPT1 pathway. Food & nutrition research 15 32577118
2020 MiRNA-324-5p inhibits inflammatory response of diabetic vessels by targeting CPT1A. European review for medical and pharmacological sciences 15 33378033
2007 Lack of association of CPT1A polymorphisms or haplotypes on hepatic lipid content or insulin resistance in Japanese individuals with type 2 diabetes mellitus. Metabolism: clinical and experimental 15 17445541
2024 TM7SF2-induced lipid reprogramming promotes cell proliferation and migration via CPT1A/Wnt/β-Catenin axis in cervical cancer cells. Cell death discovery 14 38693136
2012 A Novel Mutation in CPT1A Resulting in Hepatic CPT Deficiency. JIMD reports 14 23430932
2024 RNF5 exacerbates steatotic HCC by enhancing fatty acid oxidation via the improvement of CPT1A stability. Cancer letters 13 39734009
2015 The Origin and Diversity of Cpt1 Genes in Vertebrate Species. PloS one 13 26421611