Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae
| Autor: | Wenxi Yu, Maik Hüttemann, Shyamalagauri Jadhav, Michael Salsaa, Jenney Liu, Miriam L. Greenberg, Bianca Pereira |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Bioenergetics Saccharomyces cerevisiae lcsh:Medicine Oxidative phosphorylation Pharmacology Biochemistry Article Oxidative Phosphorylation Mice 03 medical and health sciences Medical research Oxygen Consumption 0302 clinical medicine medicine Animals Cytochrome c oxidase Glycolysis lcsh:Science Multidisciplinary biology Chemistry Valproic Acid lcsh:R biology.organism_classification Yeast Mitochondria 030104 developmental biology Mechanism of action Prostaglandin-Endoperoxide Synthases Toxicity biology.protein lcsh:Q medicine.symptom Energy Metabolism 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The widely used mood stabilizer valproate (VPA) causes perturbation of energy metabolism, which is implicated in both the therapeutic mechanism of action of the drug as well as drug toxicity. To gain insight into these mechanisms, we determined the effects of VPA on energy metabolism in yeast. VPA treatment increased levels of glycolytic intermediates, increased expression of glycolysis genes, and increased ethanol production. Increased glycolysis was likely a response to perturbation of mitochondrial function, as reflected in decreased membrane potential and oxygen consumption. Interestingly, yeast, mouse liver, and isolated bovine cytochrome c oxidase were directly inhibited by the drug, while activities of other oxidative phosphorylation complexes (III and V) were not affected. These findings have implications for mechanisms of therapeutic action and toxicity. |
| Databáze: | OpenAIRE |
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