Affinage

HADHA

Trifunctional enzyme subunit alpha, mitochondrial · UniProt P40939

Length
763 aa
Mass
83.0 kDa
Annotated
2026-06-10
79 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HADHA encodes the α-subunit of the mitochondrial trifunctional protein (TFP), an inner-membrane enzyme that carries out long-chain fatty acid β-oxidation and is incorporated into the assembled TFP complex where it is required for palmitate oxidation, ketone (β-hydroxybutyrate) production, and resistance to oxidative stress (PMID:31604922, PMID:39283617). Beyond its canonical catalytic role, HADHA functions as a monolysocardiolipin acyltransferase-like enzyme essential for cardiolipin remodeling and mitochondrial cristae integrity, such that its loss in cardiomyocytes disrupts the proton gradient, calcium dynamics, and repolarization (PMID:31604922). HADHA also acts as a respiratory supercomplex assembly factor, physically coupling FAO to oxidative phosphorylation; its loss reduces supercomplex assembly and OXPHOS and aggravates hepatic steatosis (PMID:39488787). Its metabolic output feeds epigenetic and signaling programs: β-oxidation-derived acetyl-CoA sustains H3K27 acetylation and JAK/STAT3 activation (PMID:40750765), while HADHA-generated β-hydroxybutyrate inhibits HDAC7 to drive FOXO1 nuclear exclusion and suppress hepatic gluconeogenesis (PMID:35046401). HADHA expression and activity are heavily controlled: transcriptionally by GATA4 downstream of SIRT1, by Zfp335 in regulatory T cells, and by KDM6B-dependent H3K27 demethylation (PMID:41872163, PMID:37843279, PMID:39569625); and post-translationally by a dense modification network including GCN5L1-mediated acetylation reversed by SIRT3 (PMID:30323061), lactylation at K166/K728 reversed by SIRT1/SIRT3 (PMID:40575877), succinylation reversed by SIRT5 (PMID:37688624), SUMOylation reversed by SENP3 in competition with ubiquitination (PMID:40320039), and UBE2O-mediated ubiquitination and degradation (PMID:36273042). These regulatory inputs position HADHA at the center of FAO-dependent phenotypes across tissues, including ferroptosis suppression in aging hearts via the GPX4 axis (PMID:41872163), NLRP3 inflammasome control through K255 acetylation (PMID:37625146), primary ciliogenesis through acetyl-CoA supply (PMID:41120337), and tumor metabolic reprogramming (PMID:36273042, PMID:39039194, PMID:40750765). The TFP α-subunit is encoded at chromosome 2p23 adjacent to HADHB and belongs to the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase family (PMID:9605857).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 Medium

    Established the genomic and family identity of HADHA as the α-subunit of the mitochondrial trifunctional protein, framing it as a fatty acid β-oxidation multienzyme component.

    Evidence FISH chromosomal mapping placing HADHA and HADHB adjacently at 2p23

    PMID:9605857

    Open questions at the time
    • Mapping alone does not establish catalytic activity or in vivo function
    • No information on TFP complex stoichiometry or assembly
  2. 2015 Low

    Raised the possibility of an extra-canonical role by linking HADHA to the Dicer/RISC machinery in miRNA maturation.

    Evidence Co-IP of HADHA with Dicer plus precursor/mature miRNA quantification on HADHA over/knockdown

    PMID:26367179

    Open questions at the time
    • Single Co-IP and expression-level data without reconstitution or mutagenesis
    • No mechanism for how a β-oxidation enzyme would assist miRNA processing
    • Not independently confirmed
  3. 2017 Medium

    Reported a cytosolic, non-mitochondrial pool of HADHA interacting with LC3, implicating it in long-chain fatty acid-induced autophagy.

    Evidence GFP-LC3 IP/MS, cellular fractionation, and HADHA/LC3/TOM20 co-localization under palmitic acid in intestinal epithelial cells

    PMID:28153718

    Open questions at the time
    • No functional mutagenesis or reconstitution of the autophagy role
    • Single lab; cytosolic localization not corroborated elsewhere in the corpus
  4. 2018 High

    Defined acetylation as a tunable activity switch for HADHA, mapping GCN5L1-dependent sites and SIRT3 as the opposing eraser controlling FAO and hepatic lipid handling.

    Evidence Proteomic acetyl-site mapping (K350/K383/K406), GCN5L1 knockdown/knockout and overexpression mouse models with FAO enzyme assays

    PMID:30323061

    Open questions at the time
    • Structural basis of how acetylation alters catalysis not resolved
    • Does not address other modification types competing at these sites
  5. 2019 High

    Demonstrated that HADHA is not only a β-oxidation enzyme but a monolysocardiolipin acyltransferase-like enzyme required for cardiolipin remodeling and cristae integrity, explaining its essentiality for cardiomyocyte function.

    Evidence HADHA-mutant hiPSC-derived cardiomyocytes with cardiolipin profiling, metabolic flux, calcium imaging, and proton gradient measurement

    PMID:31604922

    Open questions at the time
    • Acyltransferase active site/mechanism not biochemically dissected
    • Relationship between the two enzymatic functions unresolved
  6. 2022 High

    Connected HADHA β-oxidation output to metabolic signaling by showing ketone-mediated HDAC7 inhibition drives FOXO1 exclusion and gluconeogenesis suppression, and established UBE2O as a degradative regulator in liver cancer.

    Evidence Stable isotope tracing with HADHA OE/KD mouse models and HDAC7/FOXO1 assays; Co-IP, ubiquitination assays, and Ube2o-KO hepatocarcinogenesis mice

    PMID:35046401 PMID:36273042

    Open questions at the time
    • Quantitative contribution of HADHA-derived BHB versus other sources not delineated
    • UBE2O ubiquitination sites on HADHA not mapped
  7. 2023 Medium

    Expanded the regulatory and pathological scope of HADHA: K255 acetylation links it to NLRP3 inflammasome assembly, SIRT5 controls succinylation-coupled autophagy, and Zfp335 transcriptionally sustains HADHA for Treg metabolic differentiation.

    Evidence HFD K255 site-blocking with NLRP3/ASC imaging; MS succinyl-site mapping with SIRT5 binding/rescue; Zfp335-KO Tregs with ChIP and OXPHOS/suppression assays

    PMID:37625146 PMID:37688624 PMID:37843279

    Open questions at the time
    • Mechanistic link between K255 acetylation and ASC recruitment not structurally defined
    • Succinylation findings from a single lab without reciprocal validation
    • How HADHA metabolic state feeds back on Zfp335 not addressed
  8. 2024 High

    Established HADHA as a respiratory supercomplex assembly factor coupling FAO to OXPHOS, and linked its acetyl-CoA output to H3K27ac-driven JAK/STAT3 signaling and tumor growth, alongside MDM2/p53 modulation in glioma.

    Evidence Proteomics + BN-PAGE in HADHA-KD/KO MEFs and HFD mice; acetyl-CoA/H3K27ac ChIP and JAK/STAT3 assays; HADHA–MDM2 Co-IP with p53 epistasis and KDM6B ChIP-seq

    PMID:39039194 PMID:39488787 PMID:39569625 PMID:40750765

    Open questions at the time
    • Stoichiometry and binding interface of HADHA within supercomplexes unknown
    • Whether HADHA–MDM2 and acetyl-CoA/epigenetic effects are separable not resolved
  9. 2025 Medium

    Consolidated HADHA as a hub whose levels are set by competing SUMO/ubiquitin crosstalk (SENP3/USP10) and SIRT1→GATA4 transcription, with downstream control of ferroptosis, ciliogenesis, and lactylation-regulated activity.

    Evidence SENP3–HADHA–USP10 complex Co-IP and deSUMOylation assays; cardiomyocyte HADHA-KD mice with GPX4/ferrostatin-1; HADHA-KO with E510Q mutant and acetate rescue of cilia; K166/K728 lactylation mutagenesis in septic heart

    PMID:40320039 PMID:40575877 PMID:41120337 PMID:41872163

    Open questions at the time
    • SUMO/ubiquitin acceptor lysines and their overlap not fully mapped
    • Direct mechanism linking acetyl-CoA supply to ciliary signaling unresolved
    • Several phenotype links are single-lab
  10. 2026 Medium

    Identified HADHA as a direct small-molecule target, with melatonin binding HADHA to enhance PGC-1α and mitochondrial biogenesis in fatty liver.

    Evidence CETSA for direct melatonin–HADHA binding and HADHA knockdown rescue in MASLD models

    PMID:42118212

    Open questions at the time
    • Binding site and effect on enzymatic activity not defined
    • Mechanism connecting HADHA binding to PGC-1α induction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dense post-translational modification network (acetylation, lactylation, succinylation, SUMOylation, ubiquitination) is integrated to set HADHA activity, stability, and localization in a tissue-specific manner remains unresolved.
  • No structural model integrating modification sites with the catalytic and acyltransferase activities
  • Crosstalk hierarchy among modifications not established
  • Mechanism of the reported cytosolic/non-mitochondrial functions not reconciled with mitochondrial role

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 2 GO:0016740 transferase activity 1 GO:0016829 lyase activity 1 GO:0016853 isomerase activity 1
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1852241 Organelle biogenesis and maintenance 1 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
GCN5L1HDAC7LC3MDM2SENP3SIRT3SIRT5UBE2O
Complex memberships
SENP3-HADHA-USP10 complexmitochondrial respiratory supercomplexmitochondrial trifunctional protein (TFP)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 HADHA (TFPα) is required for fatty acid beta-oxidation and cardiolipin remodeling in human cardiomyocytes; HADHA-deficient iPSC-derived cardiomyocytes showed defective calcium dynamics, repolarization kinetics, reduced mitochondrial proton gradient, disrupted cristae structure, and defective cardiolipin remodeling. HADHA was identified as a monolysocardiolipin acyltransferase-like enzyme essential for functional mitochondria. hiPSC-derived cardiomyocytes from HADHA-mutant cells, single-cell RNA-seq, functional metabolic assays (fatty acid beta-oxidation, mitochondrial proton gradient), cardiolipin profiling, engineered microRNA maturation cocktail Nature communications High 31604922
2018 GCN5L1 acetylates HADHA at lysine residues K350, K383, and K406, and this hyperacetylation correlates with increased HADHA activity. SIRT3 opposes this by deacetylating HADHA. GCN5L1 knockdown reduces HADHA acetylation and increases fatty acid oxidation enzyme activities; liver-specific GCN5L1 knockout mice lack HADHA hyperacetylation and are protected from hepatic lipid accumulation on high-fat diet. Proteomic identification of acetylation sites, transgenic GCN5L1 overexpression mouse model, liver-specific GCN5L1 knockout mice, stable GCN5L1 knockdown in HepG2 cells, fatty acid oxidation enzyme activity assays The Journal of biological chemistry High 30323061
2022 HADHA promotes ketone body (β-hydroxybutyrate, BHB) production via β-oxidation, and BHB suppresses hepatic gluconeogenesis by selectively inhibiting HDAC7 activity via interaction with HDAC7 Glu543, facilitating FOXO1 nuclear exclusion. Liver-specific HADHA overexpression reversed hepatic gluconeogenesis in mice; HADHA knockdown augmented glucagon response. Stable isotope tracing, liver-specific HADHA overexpression and knockdown mouse models, HDAC7 activity assays, FOXO1 localization studies, high-fat diet mouse model Nature communications High 35046401
2022 UBE2O (an E2 ubiquitin-conjugating enzyme) interacts with HADHA and mediates its ubiquitination and proteasomal degradation, thereby reducing HADHA protein levels and modulating lipid metabolic reprogramming in hepatocellular carcinoma. Co-immunoprecipitation, ubiquitination assays, UBE2O overexpression/knockdown in vitro and in vivo, liver-specific Ube2o knockout mice with DEN-induced hepatocarcinogenesis Oncogene High 36273042
2025 HADHA is lactylated at K166 and K728 in septic heart tissue; lactylation at these sites inhibits HADHA activity, disturbs mitochondrial function, reduces ATP production, impairs energy metabolism, and reduces cardiomyocyte contraction force. SIRT1 and SIRT3 were identified as erasers of HADHA lactylation at these sites. Proteomic analysis of lactylation sites in septic rat heart tissues, LPS-induced cardiomyocyte model, K166/K728 site-directed mutagenesis, mitochondrial function assays, ATP measurements, transcriptomic and metabolomic analyses, in vivo cardiac function measurement Circulation research High 40575877
2023 Acetylation of HADHA at K255 (in obese mouse hearts, promoted by mitochondrial hyperacetylation) triggers mitochondrial localization of ASC and facilitates NLRP3 inflammasome assembly. Blockade of K255 acetylation suppressed the NLRP3 inflammasome and attenuated post-ischemia/reperfusion myocardial fibrosis in obese mice. High-fat diet mouse model, K255 acetylation site identification, site-specific blocking experiments, NLRP3 inflammasome assembly assays (ASC localization by imaging), post-I/R myocardial fibrosis assessment Diabetes Medium 37625146
2023 HADHA succinylation (induced by morphine) is reversed by the desuccinylase SIRT5, which selectively binds HADHA. SIRT5-mediated HADHA desuccinylation reduced P62 expression and alleviated morphine tolerance, linking HADHA succinylation to autophagy dysregulation. LC-MS/MS and parallel reaction monitoring for succinylation site mapping, SIRT5 binding assay, SIRT5 overexpression in intrathecal morphine rat model, P62/LC3 autophagy marker measurement Naunyn-Schmiedeberg's archives of pharmacology Medium 37688624
2024 KDM6B demethylates histone H3K27 at the HADHA locus to activate HADHA transcription during cementoblast mineralization. Additionally, lactylation of HADHA (at specific sites identified by lactylation proteomics) promotes FAO and mineralization; KDM6B regulates HADHA lactylation. Co-immunoprecipitation confirmed interaction between lactylated HADHA and its partners. ChIP-seq, RNA-seq, ChIP-qPCR, HADHA overexpression rescue experiments, lactylation proteomics, Co-IP, FAO activity assays, in vivo KDM6B inhibition in mice Journal of dental research Medium 39569625
2024 HADHA participates in respiratory supercomplex (SC) assembly and couples FAO to OXPHOS. HADHA knockdown cells and HADHA-knockout MEFs displayed reduced SC assembly and defective OXPHOS. HADHA expression is upregulated when OXPHOS is stimulated (glucose-to-galactose switch) or lipid metabolism is induced (high-fat diet). HADHA heterozygous mice on HFD showed enhanced steatosis with reduced SC assembly and OXPHOS. Proteomics identifying HADHA as SC assembly factor, HADHA-KD cells and HADHA-KO MEFs with SC assembly assays (BN-PAGE), galactose medium OXPHOS stimulation, HFD mouse model with SC assembly analysis Advanced science High 39488787
2023 Zfp335 transcription factor controls effector Treg (eTreg) differentiation by directly targeting the FAO enzyme Hadha to maintain fatty acid oxidation and oxidative phosphorylation in Tregs. Zfp335-deficient Tregs showed reduced HADHA expression, dysfunctional mitochondrial activity, and failed to differentiate into eTregs. Treg-specific Zfp335 knockout mice, scRNA-seq, chromatin immunoprecipitation (direct Hadha targeting), OXPHOS assays, Treg functional suppression assays The Journal of clinical investigation High 37843279
2017 HADHA protein is present not only in mitochondria but also in the cytosol. HADHA was identified as an LC3-interacting protein in intestinal epithelial cells via immunoprecipitation with a GFP-LC3 antibody. LC3 puncta co-localized with HADHA (but not with the mitochondrial marker TOM20) and were enhanced by palmitic acid stimulation, suggesting HADHA has extra-mitochondrial roles in long-chain fatty acid-induced autophagy. GFP-LC3 immunoprecipitation followed by mass spectrometry, cellular fractionation, immunofluorescence co-localization (HADHA vs. LC3 vs. TOM20), palmitic acid treatment of IEC lines Biochemical and biophysical research communications Medium 28153718
2015 HADHA associates with the human Dicer complex (RNA-induced silencing machinery). Immunoprecipitation showed HADHA co-precipitates with Dicer; HADHA overexpression increased mature miRNA levels with corresponding decrease in precursor miRNA, while HADHA knockdown had the opposite effect, suggesting an auxiliary role in miRNA biogenesis. Co-immunoprecipitation of HADHA with Dicer, immunohistochemical co-localization with Dicer in cytoplasm, HADHA overexpression/knockdown with miRNA precursor and mature miRNA quantification Biochemical and biophysical research communications Low 26367179
1997 HADHA and HADHB genes (encoding the α and β subunits of the mitochondrial trifunctional protein) are both located on human chromosome band 2p23 and are in close proximity, analogous to the operon-like arrangement of bacterial fatty acid beta-oxidation multienzyme complex genes. The α subunit (HADHA) belongs to the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase family. Fluorescence in situ hybridization (FISH) chromosomal mapping Cytogenetics and cell genetics Medium 9605857
2025 HADHA deficiency impairs primary ciliogenesis: HADHA-knockout cells showed reduced ciliary frequency and length and decreased ciliary signaling mediators. The dehydrogenase-deficient E510Q mutant of HADHA failed to rescue ciliogenesis in KO cells, unlike wild-type HADHA reintroduction. Supplementation with sodium acetate (to restore intracellular acetyl-CoA) rescued primary cilia in HADHA-deficient cells, linking HADHA's β-oxidation activity and acetyl-CoA production to ciliogenesis. HADHA knockout cell line, wild-type and E510Q mutant HADHA rescue transfection, ciliary frequency and length quantification, sodium acetate supplementation rescue experiment Scientific reports Medium 41120337
2024 HADHA interacts with MDM2 and accelerates MDM2-mediated p53 ubiquitination in glioma cells. Co-immunoprecipitation confirmed HADHA–MDM2 physical interaction. MDM2 knockdown or p53 overexpression attenuated the pro-tumorigenic effects of HADHA overexpression. Co-immunoprecipitation, protein stability assays, HADHA knockdown/overexpression in glioma cells, MDM2 knockdown and p53 overexpression epistasis experiments, in vivo xenograft Cancer gene therapy Medium 39039194
2025 SIRT1 deficiency in aging hearts reduces HADHA expression through inhibition of the transcription factor GATA4 (which activates HADHA transcription). HADHA deficiency induces mitochondrial dysfunction, excessive ROS, glutathione depletion, GPX4 suppression, and ferroptosis. Cardiomyocyte-specific HADHA knockdown in young mice recapitulates ferroptotic cardiac remodeling reversible by ferrostatin-1. SIRT1 activation by resveratrol restores HADHA expression and suppresses ferroptosis. Cardiomyocyte-specific HADHA knockdown mice, rAAV9-mediated cardiac SIRT1 overexpression, proteomic analysis, GATA4 transcriptional regulation of HADHA, ferrostatin-1 rescue, lipid peroxidation and GPX4 assays Cell death & disease Medium 41872163
2025 SENP3 interacts with HADHA and catalyzes its deSUMOylation at two lysine residues. SUMOylation and ubiquitination compete at the same modification sites on HADHA, influencing protein stability and consequently regulating FAO levels. A physical complex of SENP3, HADHA, and USP10 was identified. HADHA deSUMOylation by SENP3 enhanced chemotherapy sensitivity in intrahepatic cholangiocarcinoma. Co-immunoprecipitation (SENP3–HADHA–USP10 complex), deSUMOylation assay, lipidomics profiling, patient-derived organoid drug screening, in vitro and in vivo chemotherapy sensitivity assays Cancer letters Medium 40320039
2024 HADHA regulates the JAK/STAT3 signaling pathway through modulation of H3K27ac histone acetylation in glioblastoma. HADHA knockdown decreases acetyl-CoA levels, reducing H3K27ac modification and inhibiting JAK/STAT3 activation, linking HADHA's enzymatic production of acetyl-CoA to epigenetic regulation. HADHA knockdown in GBM cells, acetyl-CoA measurement, H3K27ac ChIP, JAK/STAT3 pathway activity assays, in vitro and in vivo tumor growth assays with JIB-04 inhibitor Cell death discovery Medium 40750765
2025 HADHA interacts with SP1 in esophageal cancer cells and induces MDM2 expression. HADHA also activates mTOR signaling. RNA profiling after HADHA knockdown showed significant suppression of mTOR signaling. Co-immunoprecipitation (HADHA–SP1 interaction), HADHA knockdown with RNA profiling, MDM2 expression analysis, in vitro and in vivo tumor growth assays Acta biochimica et biophysica Sinica Low 39327932
2024 LCHADD iPSC-derived RPE cells expressing a wildtype HADHA copy via rAAV incorporated TFPα-FLAG into the TFP complex in the mitochondria, accumulated less 3-hydroxyacylcarnitines, released more ketones in response to palmitate, and were more resistant to oxidative stress. This demonstrates that HADHA is incorporated into the mitochondrial TFP complex and is required for palmitate oxidation and ketone production in RPE cells. iPSC-derived RPE from LCHADD patients, rAAV-HADHA transduction, mitochondrial fractionation, 3-hydroxyacylcarnitine quantification, palmitate oxidation and ketone release assays, DHA-induced oxidative stress rescue Investigative ophthalmology & visual science Medium 39283617
2026 Melatonin directly binds HADHA (validated by CETSA) and enhances PGC-1α expression, promoting mitochondrial biogenesis and lipid metabolism in hepatocytes. HADHA knockdown abrogated the beneficial effects of melatonin on lipid accumulation in MASLD models. Cellular thermal shift assay (CETSA) for direct melatonin–HADHA binding, HADHA knockdown with melatonin treatment, PGC-1α expression measurement, lipid accumulation assays in mouse MASLD model and palmitic acid-treated hepatocytes Molecular biomedicine Medium 42118212

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 TFPa/HADHA is required for fatty acid beta-oxidation and cardiolipin re-modeling in human cardiomyocytes. Nature communications 96 31604922
2020 MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming. Journal of hematology & oncology 81 32033570
2018 The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial β-oxidation enzyme HADHA. The Journal of biological chemistry 76 30323061
2006 Transcriptional studies and regulatory interactions between the phoR-phoP operon and the phoU, mtpA, and ppk genes of Streptomyces lividans TK24. Journal of bacteriology 64 16385057
2006 Metabolic control during exercise with and without medium-chain triglycerides (MCT) in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Molecular genetics and metabolism 63 16876451
2022 The mitochondrial β-oxidation enzyme HADHA restrains hepatic glucagon response by promoting β-hydroxybutyrate production. Nature communications 60 35046401
2005 Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency. Journal of inherited metabolic disease 53 15902556
2011 Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency. Molecular genetics and metabolism 46 21549624
2000 Heterozygosity for the common LCHAD mutation (1528g>C) is not a major cause of HELLP syndrome and the prevalence of the mutation in the Dutch population is low. Pediatric research 46 10926288
2010 Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain. Neurochemistry international 35 20381565
2010 Urgent metabolic service improves survival in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency detected by symptomatic identification and pilot newborn screening. Journal of inherited metabolic disease 32 21103935
2007 Identification of novel mutations of the HADHA and HADHB genes in patients with mitochondrial trifunctional protein deficiency. International journal of molecular medicine 30 17143551
2006 Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Molecular genetics and metabolism 29 16996288
2022 UBE2O promotes lipid metabolic reprogramming and liver cancer progression by mediating HADHA ubiquitination. Oncogene 28 36273042
2011 HADHA is a potential predictor of response to platinum-based chemotherapy for lung cancer. Asian Pacific journal of cancer prevention : APJCP 27 22471497
2010 Disturbance of mitochondrial energy homeostasis caused by the metabolites accumulating in LCHAD and MTP deficiencies in rat brain. Life sciences 26 20399795
2010 A comprehensive HADHA c.1528G>C frequency study reveals high prevalence of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency in Poland. Journal of inherited metabolic disease 26 20814823
2019 HADHA and HADHB gene associated phenotypes - Identification of rare variants in a patient cohort by Next Generation Sequencing. Molecular and cellular probes 25 30682426
2014 Mitochondrial bioenergetics deregulation caused by long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies in rat brain: a possible role of mPTP opening as a pathomechanism in these disorders? Biochimica et biophysica acta 25 24946182
2021 Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells. Scientific reports 24 34168259
2017 High prevalence of carriers of variant c.1528G>C of HADHA gene causing long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the population of adult Kashubians from North Poland. PloS one 24 29095929
2016 Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle. Toxicology in vitro : an international journal published in association with BIBRA 24 27371118
2019 Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma. Laboratory investigation; a journal of technical methods and pathology 23 31527828
2019 HADHA overexpression disrupts lipid metabolism and inhibits tumor growth in clear cell renal cell carcinoma. Experimental cell research 22 31472118
2025 Lactylation of HADHA Promotes Sepsis-Induced Myocardial Depression. Circulation research 21 40575877
2022 HADHA alleviates hepatic steatosis and oxidative stress in NAFLD via inactivation of the MKK3/MAPK pathway. Molecular biology reports 21 36376538
2022 Silencing of Mitochondrial Trifunctional Protein A Subunit (HADHA) Increases Lipid Stores, and Reduces Oviposition and Flight Capacity in the Vector Insect Rhodnius prolixus. Frontiers in insect science 21 38468769
2018 Fatal pitfalls in newborn screening for mitochondrial trifunctional protein (MTP)/long-chain 3-Hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. Orphanet journal of rare diseases 20 30029694
2017 HADHA, the alpha subunit of the mitochondrial trifunctional protein, is involved in long-chain fatty acid-induced autophagy in intestinal epithelial cells. Biochemical and biophysical research communications 20 28153718
2023 Obesity Enables NLRP3 Activation and Induces Myocardial Fibrosis via Hyperacetylation of HADHa. Diabetes 19 37625146
2014 Sports in LCHAD Deficiency: Maximal Incremental and Endurance Exercise Tests in a 13-Year-Old Patient with Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency (LCHADD) and Heptanoate Treatment. JIMD reports 19 24997711
2012 A faster, high resolution, mtPA-GFP-based mitochondrial fusion assay acquiring kinetic data of multiple cells in parallel using confocal microscopy. Journal of visualized experiments : JoVE 17 22847388
2012 Association of HADHA expression with the risk of breast cancer: targeted subset analysis and meta-analysis of microarray data. BMC research notes 16 22240105
2003 Accumulation of 3-hydroxy-fatty acids in the culture medium of long-chain L-3-hydroxyacyl CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein-deficient skin fibroblasts: implications for medium chain triglyceride dietary treatment of LCHAD deficiency. Pediatric research 16 12621125
2023 A G1528C Hadha knock-in mouse model recapitulates aspects of human clinical phenotypes for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Communications biology 15 37644104
2010 Paternal isodisomy of chromosome 2 as a cause of long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. American journal of medical genetics. Part A 14 20583174
2021 Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations. Molecular medicine reports 11 34878152
1997 Fluorescence in situ hybridization mapping of the alpha and beta subunits (HADHA and HADHB) of human mitochondrial fatty acid beta-oxidation multienzyme complex to 2p23 and their evolution. Cytogenetics and cell genetics 11 9605857
2023 Zfp335 establishes eTreg lineage and neonatal immune tolerance by targeting Hadha-mediated fatty acid oxidation. The Journal of clinical investigation 10 37843279
2024 HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 39488787
2024 KDM6B-Mediated HADHA Demethylation/Lactylation Regulates Cementogenesis. Journal of dental research 9 39569625
2008 Acute fatty liver of pregnancy and neonatal long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency. European journal of pediatrics 9 18408953
1999 Long-chain L 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency does not appear to be the primary cause of lipid myopathy in patients with Bannayan-Riley-Ruvalcaba syndrome (BRRS). American journal of medical genetics 9 10076877
2025 SENP3 induced HADHA deSUMOylation enhances intrahepatic cholangiocarcinoma chemotherapy sensitivity via fatty acid oxidation. Cancer letters 8 40320039
2016 An Unusual Case of LCHAD Deficiency Presenting With a Clinical Picture of Hemophagocytic Lymphohistiocytosis: Secondary HLH or Coincidence? Journal of pediatric hematology/oncology 8 27769081
1996 Improved detection of the G1528C mutation in LCHAD deficiency. Biochemical and molecular medicine 8 8809345
2020 Deep geno- and phenotyping in two consanguineous families with CMT2 reveals HADHA as an unusual disease-causing gene and an intronic variant in GDAP1 as an unusual mutation. Journal of neurology 7 32897397
2022 A novel HADHA variant associated with an atypical moderate and late-onset LCHAD deficiency. Molecular genetics and metabolism reports 6 35782617
2014 Use of propofol for short duration procedures in children with long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiencies. Molecular genetics and metabolism 6 24780638
2009 EFFECT OF FEEDING, EXERCISE AND GENOTYPE ON PLASMA 3-HYDROXYACYLCARNITINES IN CHILDREN WITH LCHAD DEFICIENCY. Topics in clinical nutrition 6 20589231
2023 HADHA promotes ovarian cancer outgrowth via up-regulating CDK1. Cancer cell international 5 37986001
2017 Scale up and pharmacokinetic study of a novel mutated chimeric tissue plasminogen activator (mt-PA) in rats. Scientific reports 5 28223717
2015 Association of HADHA with human RNA silencing machinery. Biochemical and biophysical research communications 5 26367179
2025 Cardiomyopathy in a c.1528G>C Hadha mouse is associated with cardiac tissue lipotoxicity and altered cardiolipin species. Journal of lipid research 4 40164334
2023 Morphine induces HADHA succinylation, while HADHA desuccinylation alleviates morphine tolerance by influencing autophagy. Naunyn-Schmiedeberg's archives of pharmacology 4 37688624
2020 Retinitis pigmentosa as a clinical presentation of LCHAD deficiency: A clinical case and review of the literature. Archivos de la Sociedad Espanola de Oftalmologia 4 34479707
2015 [The changes of LCHAD in preeclampsia with different clinical features and the correlation with NADPH P47-phox, p38MAPK-α, COX-2 and serum FFA and TG]. Zhonghua fu chan ke za zhi 4 25877604
2006 Identification of a novel single nucleotide polymorphism of HADHA gene at a referred primer-binding site during pre-diagnostic tests for preimplantation genetic diagnosis. Journal of Korean medical science 4 17043408
2025 Methanol chemoreceptor MtpA- and flagellin protein FliC-dependent methylotaxis contributes to the spatial colonization of PPFM in the phyllosphere. ISME communications 3 40584553
2024 iPSC-Derived LCHADD Retinal Pigment Epithelial Cells Are Susceptible to Lipid Peroxidation and Rescued by Transfection of a Wildtype AAV-HADHA Vector. Investigative ophthalmology & visual science 3 39283617
2019 RETINAL PHENOTYPE IN A CASE OF LCHAD/TFP DEFICIENCY WITH LATE-STAGE DIAGNOSIS. Retinal cases & brief reports 3 28301411
2018 In silico and in vivo analyses of the mutated human tissue plasminogen activator (mtPA) and the antithetical effects of P19 silencing suppressor on its expression in two Nicotiana species. Scientific reports 3 30232346
2016 Diagnosis of LCHAD/TFP deficiency in an at risk newborn using umbilical cord blood acylcarnitine analysis. Molecular genetics and metabolism reports 3 27995076
2025 HADHA promotes apoptosis and inflammatory response in bovine endometrial epithelial cells by regulating transcription and metabolism. International journal of biological macromolecules 2 39952496
2024 HADHA promotes glioma progression by accelerating MDM2-mediated p53 ubiquitination. Cancer gene therapy 2 39039194
2023 An Autopsy Analysis of a Patient With Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency Caused by Compound Heterozygous HADHA Gene Mutations. The American journal of forensic medicine and pathology 2 37549033
2005 Homogeneous amplification nucleobase quenching assay to detect the E474Q LCHAD deficiency mutation. Genetic testing 2 15857179
2025 HADHA-mediated regulation of JAK/STAT3 signaling in glioblastoma: a metabolic-epigenetic axis. Cell death discovery 1 40750765
2025 Mitochondrial Trifunctional Protein Deficiency due to HADHA Variants Masquerading as Charcot-Marie-Tooth Disease. Journal of the peripheral nervous system : JPNS 1 40790338
2025 Early-Onset Sensorimotor Axonal Neuropathy as Sole Manifestation of HADHA-Related Disorder/ Mitochondrial Trifunctional Protein Defect. Journal of child neurology 1 40820380
2024 HADHA promotes esophageal cancer progression by activating mTOR signaling and the SP1/MDM2 axis. Acta biochimica et biophysica Sinica 1 39327932
2024 Peripheral Neuropathy in Mitochondrial Trifunctional Protein Deficiency due to a Variant in HADHA Gene. Iranian journal of pathology 1 39687448
2021 Generation of an induced pluripotent stem cell line, ICGi028-A, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.E510Q mutation in HADHA. Stem cell research 1 33887580
2010 [EBV infection revealing a long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in a 3-year-old boy]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 1 21035315
2026 SIRT1 deficiency promotes age-related heart failure through enhancing ferroptosis via GATA4-HADHA-GPX4 axis. Cell death & disease 0 41872163
2026 Melatonin targets mitochondrial trifunctional enzyme HADHA to improve lipid metabolism in metabolic dysfunction-associated steatotic liver disease. Molecular biomedicine 0 42118212
2025 Disrupting mitochondrial β-oxidation by depletion of HADHA impairs primary ciliogenesis. Scientific reports 0 41120337
2022 [HADHA Inhibits the Migration and Invasion of HTR-8/SVneo Cells by Regulating PI3K/AKT Signaling Pathway]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 36224682
2015 [Study on the methylation of LCHAD gene promoter region in mitochondria of trophoblast cells incubated with long-chain fatty acids]. Zhonghua yi xue za zhi 0 26711077

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