ArticleNature communications2019
TFPa/HADHA is required for fatty acid beta-oxidation and cardiolipin re-modeling in human cardiomyocytes.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 81 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation.Frontiers in cardiovascular medicine · 2022Pooled it
- Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension with HADHA-associated improvements in fatty acid oxidation and mitochondrial redox homeostasis.Redox biology · 2026Article
- Mitochondrial-targeted SS-31 peptide attenuates radiation-induced cardiomyocyte senescence.Journal of radiation research · 2026Article
- Intermediate accumulated upon interruption of fatty acid oxidation flux promotes tumoral ferroptosis and improves immunotherapy.Nature communications · 2026Article
- Differential expression of metabolic genes distinguishes physiological from pathological cardiac hypertrophy.BMC cardiovascular disorders · 2026Article
- Comparative Hepatic Transcriptomic Analysis Reveals Metabolic Regulatory Differences Between Qilian and Oula Sheep.Veterinary sciences · 2026Article
- Melatonin targets mitochondrial trifunctional enzyme HADHA to improve lipid metabolism in metabolic dysfunction-associated steatotic liver disease.Molecular biomedicine · 2026Article
- Alternative splicing and polyadenylation facilitate transcriptome diversity underlying high-altitude adaptation in pigs.Communications biology · 2026Article
- Early blood DNA methylation patterns associated with glycemic progression in a prospective Indian cohort.Clinical epigenetics · 2026Article
- Advanced physiological maturation of human iPSC-derived cardiomyocytes using an algorithm-directed optimization of defined media components.Nature communications · 2026Article
- SIRT1 deficiency promotes age-related heart failure through enhancing ferroptosis via GATA4-HADHA-GPX4 axis.Cell death & disease · 2026Article
- Cardiolipin Remodeling as a Regulatory Switch in Osteogenesis: Insights from Multimodal Metabolic Imaging and Molecular Profiling.bioRxiv : the preprint server for biology · 2025Article
- GLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function.Nature communications · 2025Article
- Metabolic cardiomyopathies: untangling clinical heterogeneity with human stem-cell derived models.EMBO molecular medicine · 2025Review
- Chondrocyte fatty acid oxidation drives osteoarthritis via SOX9 degradation and epigenetic regulation.Nature communications · 2025Article
- Cardiomyopathy in a c.1528G>C Hadha mouse is associated with cardiac tissue lipotoxicity and altered cardiolipin species.Journal of lipid research · 2025Article
- KDM6B-Mediated HADHA Demethylation/Lactylation Regulates Cementogenesis.Journal of dental research · 2025Article
- HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Beyond the Heartbeat: Single-Cell Omics Redefining Cardiovascular Research.Current cardiology reports · 2024Review
- Annonaceous acetogenins mimic AA005 targets mitochondrial trifunctional enzyme alpha subunit to treat obesity in male mice.Nature communications · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Mitochondrial trifunctional protein deficiency, due to mutations in hydratase subunit A (HADHA), results in sudden infant death syndrome with no cure. To reveal the disease etiology, we generated stem cell-derived cardiomyocytes from HADHA-deficient hiPSCs and accelerated their maturation via an engineered microRNA maturation cocktail that upregulated the epigenetic regulator, HOPX. Here we report, matured HADHA mutant cardiomyocytes treated with an endogenous mixture of fatty acids manifest the disease phenotype: defective calcium dynamics and repolarization kinetics which results in a pro-arrhythmic state. Single cell RNA-seq reveals a cardiomyocyte developmental intermediate, based on metabolic gene expression. This intermediate gives rise to mature-like cardiomyocytes in control cells but, mutant cells transition to a pathological state with reduced fatty acid beta-oxidation, reduced mitochondrial proton gradient, disrupted cristae structure and defective cardiolipin remodeling. This study reveals that HADHA (tri-functional protein alpha), a monolysocardiolipin acyltransferase-like enzyme, is required for fatty acid beta-oxidation and cardiolipin remodeling, essential for functional mitochondria in human cardiomyocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.