Abstract：
: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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Salsaa M,Pereira B,Liu J,Yu W,Jadhav S,Hüttemann M,Greenberg MLdoi
10.1038/s41598-020-68725-5subject
Has Abstractpub_date
2020-07-16 00:00:00pages
11785issue
1issn
2045-2322pii
10.1038/s41598-020-68725-5journal_volume
10pub_type
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