ArticleMolecular genetics and metabolism2014
Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts.
Article in Molecular genetics and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Integrated Pharmacoepigenomic Analysis Uncovers the Impact of Antiseizure Medications on Developmental Pathways and the Protective Effect of Folic Acid.International journal of molecular sciences · 2025Article
- Imaging flow cytometry reveals divergent mitochondrial phenotypes in mitochondrial disease patients.iScience · 2025Article
- Valproic Acid and Lamotrigine Differentially Modulate the Telomere Length in Epilepsy Patients.Journal of clinical medicine · 2025Article
- Preconditioning of Human Umbilical Cord Mesenchymal Stem Cells with a Histone Deacetylase Inhibitor: Valproic Acid.Balkan medical journal · 2024Article
- Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants.Arquivos de neuro-psiquiatria · 2023Article
- Mitochondrial Toxic Effects of Antiepileptic Drug Valproic Acid on Mouse Kidney Stem Cells.Toxics · 2023Article
- Mitochondrial DNA Copy Number Is Associated With Treatment Response and Cognitive Function in Euthymic Bipolar Patients Receiving Valproate.The international journal of neuropsychopharmacology · 2022Article
- Metabolic plasticity in blast crisis-chronic myeloid leukaemia cells under hypoxia reduces the cytotoxic potency of drugs targeting mitochondria.Discover oncology · 2022Article
- DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with p53.International journal of biological sciences · 2022Article
- Mitochondrial hepatopathy: Respiratory chain disorders- 'breathing in and out of the liver'.World journal of hepatology · 2021Review
- Discovery of the First Vitamin K Analogue as a Potential Treatment of Pharmacoresistant Seizures.Journal of medicinal chemistry · 2020Article
- The metabolic face of migraine - from pathophysiology to treatment.Nature reviews. Neurology · 2019Review
- Mitochondria, Metabolism, and Redox Mechanisms in Psychiatric Disorders.Antioxidants & redox signaling · 2019Review
- Review
- Analyzing the Mechanisms Behind Macrolide Antibiotic-Induced Liver Injury Using Quantitative Systems Toxicology Modeling.Pharmaceutical research · 2019Article
- Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment.Scientific reports · 2018Article
- Combination Effect of Silver Nanoparticles and Histone Deacetylases Inhibitor in Human Alveolar Basal Epithelial Cells.Molecules (Basel, Switzerland) · 2018Article
- The pharmacogenomics of valproic acid.Journal of human genetics · 2017Review
- Inherited mitochondrial genomic instability and chemical exposures.Toxicology · 2017Review
- Modulation of host central carbon metabolism and in situ glucose uptake by intracellular Trypanosoma cruzi amastigotes.PLoS pathogens · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to treat migraine, chronic headache and bipolar disorder. Although it is usually well tolerated, a severe hepatotoxic reaction has been repeatedly reported after VPA administration. A profound toxic reaction on administration of VPA has been observed in several patients carrying POLG mutations, and heterozygous genetic variation in POLG has been strongly associated with VPA-induced liver toxicity. Here we studied the effect of VPA in fibroblasts of five patients carrying pathogenic mutations in the POLG gene. VPA administration caused a significant increase in the expression of POLG and several regulators of mitochondrial biogenesis. It was further supported by elevated mtDNA copy numbers. The effect of VPA on mitochondrial biogenesis was observed in both control and patient cell lines, but the capacity of mutant POLG to increase the expression of mitochondrial genes and to increase mtDNA copy numbers was less effective. No evidence of substantive differences in DNA methylation across the genome was observed between POLG mutated patients and controls. Given the marked perturbation of gene expression observed in the cell lines studied, we conclude that altered DNA methylation is unlikely to make a major contribution to POLG-mediated VPA toxicity. Our data provide experimental evidence that VPA triggers increased mitochondrial biogenesis by altering the expression of several mitochondrial genes; however, the capacity of POLG-deficient liver cells to address the increased metabolic rate caused by VPA administration is significantly impaired.
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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.