ArticleEuropean journal of pharmacology2012
Effect of valproic acid on mitochondrial epigenetics.
Article in European journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 81 citations in OpenAlex.
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- Epigenetics and Gut Microbiota in the Pathogenesis and Treatment of Bipolar Disorder (BD).Cells · 2025Review
- From Womb to Mind: Prenatal Epigenetic Influences on Mental Health Disorders.International journal of molecular sciences · 2025Review
- Mitochondrial epigenetic mechanisms in cancer: an updated overview.Frontiers in cell and developmental biology · 2025Review
- Mitochondrial Dysfunction as a Biomarker of Illness State in Bipolar Disorder: A Critical Review.Brain sciences · 2024Review
- Therapeutic potential of tLyp-1-EV-shCTCF in inhibiting liver cancer stem cell self-renewal and immune escape via SALL3 modulation in hepatocellular carcinoma.Translational oncology · 2024Article
- Mitochondrial epigenetic modifications and nuclear-mitochondrial communication: A new dimension towards understanding and attenuating the pathogenesis in women with PCOS.Reviews in endocrine & metabolic disorders · 2023Review
- Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-International journal of molecular sciences · 2022Article
- LncRNAInternational journal of molecular sciences · 2021Review
- Mitochondrial DNA Methylation and Human Diseases.International journal of molecular sciences · 2021Review
- Mitochondrial dysfunction as a critical event in the pathophysiology of bipolar disorder.Mitochondrion · 2021Review
- Role of Mitochondria in Neurodegenerative Diseases: From an Epigenetic Perspective.Frontiers in cell and developmental biology · 2021Review
- Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy.Molecular cancer · 2020Review
- Immunoprecipitation and mass spectrometry define TET1 interactome during oligodendrocyte differentiation.Cell & bioscience · 2020Article
- Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing.International journal of molecular sciences · 2019Review
- Mitochondrial DNA: Epigenetics and environment.Environmental and molecular mutagenesis · 2019Review
- From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs.EMBO molecular medicine · 2019Review
- Early Behavioral Alterations and Increased Expression of Endogenous Retroviruses Are Inherited Across Generations in Mice Prenatally Exposed to Valproic Acid.Molecular neurobiology · 2019Article
- HDAC inhibition induces autophagy and mitochondrial biogenesis to maintain mitochondrial homeostasis during cardiac ischemia/reperfusion injury.Journal of molecular and cellular cardiology · 2019Article
- Mitoepigenetics and Neurodegenerative Diseases.Frontiers in endocrinology · 2019Review
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3 authors at 1 institution in 1 country.
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Abstract
Valproic acid (valproate), an anticonvulsant and a mood stabilizer, is a potent histone deacetylase inhibitor and a widely utilized pharmacological tool for neuroepigenetic research including DNA methylation. However, only nuclear but not mitochondrial DNA (mtDNA) has been investigated for the effects of valproate on the formation of 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5 hmC). Using mouse 3T3-L1 cells, we investigated the effects of short (1 day) and prolonged (3 days) valproate treatment on global mtDNA 5 mC content, global and mtDNA sequence-specific 5 hmC content, mRNA levels for ten-eleven-translocation (TET) enzymes involved in 5 hmC formation, and the mitochondrial content of TET proteins. Only 5 hmC but not 5 mC content in mtDNA was affected (decreased) by valproate, and only after the prolonged treatment. This action of valproate was mimicked by MS-275, a class I histone deacetylase inhibitor. The prolonged but not the short valproate treatment decreased the expression of Tet1 mRNA and reduced the mitochondrial content of the TET1 protein. Hence, a likely scenario for a valproate-induced 5 hmC decrease in mtDNA may involve nuclear histone deacetylase inhibition (mitochondria do not contain histones) causing the initial increase of Tet1 transcription, which is followed by a delayed compensatory decrease of Tet1 expression and a reduced presence of TET1 protein in mitochondria. Further research is needed to elucidate the functional implications of epigenetic modifications of mtDNA. The observed effects of valproate on mitochondrial epigenetics may have implications for a better understanding of both therapeutic and unwanted effects of this drug and possibly other histone deacetylase inhibitors.
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