ArticleJournal of inherited metabolic disease2016
Mitochondrial trifunctional protein deficiency in human cultured fibroblasts: effects of bezafibrate.
Article in Journal of inherited metabolic disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Dodecanedioic Acid: Alternative Carbon Substrate or Toxic Metabolite?Biomolecules · 2025Article
- Hypertrophic Cardiomyopathy Through the Lens of Mitochondria.Biomedicines · 2025Review
- Article
- Disturbance of Mitochondrial Dynamics, Endoplasmic Reticulum-Mitochondria Crosstalk, Redox Homeostasis, and Inflammatory Response in the Brain of Glutaryl-CoA Dehydrogenase-Deficient Mice: Neuroprotective Effects of Bezafibrate.Molecular neurobiology · 2022Article
- Peroxisome Proliferator-Activated Receptor Activation in Precision-Cut Bovine Liver Slices Reveals Novel Putative PPAR Targets in Periparturient Dairy Cows.Frontiers in veterinary science · 2022Article
- Efficacy of bezafibrate in two patients with mitochondrial trifunctional protein deficiency.Molecular genetics and metabolism reports · 2020Article
- Mitochondrial Fatty Acid Oxidation Disorders: Laboratory Diagnosis, Pathogenesis, and the Complicated Route to Treatment.Journal of lipid and atherosclerosis · 2020Review
- Using Mitochondrial Trifunctional Protein Deficiency to Understand Maternal Health.Journal of cellular signaling · 2020Article
- TFPa/HADHA is required for fatty acid beta-oxidation and cardiolipin re-modeling in human cardiomyocytes.Nature communications · 2019Article
- Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan; 2nd report QOL survey.Molecular genetics and metabolism reports · 2019Article
- Review
- Management and diagnosis of mitochondrial fatty acid oxidation disorders: focus on very-long-chain acyl-CoA dehydrogenase deficiency.Journal of human genetics · 2019Review
- Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan.Molecular genetics and metabolism reports · 2018Article
- Mitochondrial Agents for Bipolar Disorder.The international journal of neuropsychopharmacology · 2018Review
- Clinical and molecular investigation of 14 Japanese patients with complete TFP deficiency: a comparison with Caucasian cases.Journal of human genetics · 2017Article
- Short-chain acyl-CoA dehydrogenase deficiency: from gene to cell pathology and possible disease mechanisms.Journal of inherited metabolic disease · 2017Review
- Perspectives on Exertional Rhabdomyolysis.Sports medicine (Auckland, N.Z.) · 2017Review
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Authors and funding
16 authors at 12 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial trifunctional protein (MTP) deficiency caused by HADHA or HADHB gene mutations exhibits substantial molecular, biochemical, and clinical heterogeneity and ranks among the more severe fatty acid oxidation (FAO) disorders, without pharmacological treatment. Since bezafibrate has been shown to potentially correct other FAO disorders in patient cells, we analyzed its effects in 26 MTP-deficient patient fibroblasts representing 16 genotypes. Overall, the patient cell lines exhibited variable, complex, biochemical profiles and pharmacological responses. HADHA-deficient fibroblasts showed markedly reduced alpha subunit protein levels together with decreased beta-subunit abundance, exhibited a -86 to -96% defect in LCHAD activity, and produced large amounts of C14 and C16 hydroxyacylcarnitines. In control fibroblasts, exposure to bezafibrate (400 μM for 48 h) increased the abundance of HADHA and HADHB mRNAs, immune-detectable alpha and beta subunit proteins, activities of LCHAD and LCKAT, and stimulated FAO capacities, clearly indicating that MTP is pharmacologically up-regulated by bezafibrate in human fibroblasts. In MTP-deficient patient fibroblasts, which were found markedly FAO-deficient, bezafibrate improved FAO capacities in six of 26 (23%) cases, including three cell lines heterozygous for the common c1528G > C mutation. Altogether, our results strongly suggest that, due to variable effects of HADHA and HADHB mutations on MTP abundance and residual activity, improvement of MTP deficiency in response to bezafibrate was achieved in a subset of responsive genotypes.
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