ArticleThe Journal of biological chemistry2015
Perturbation of the Vacuolar ATPase: A NOVEL CONSEQUENCE OF INOSITOL DEPLETION.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Oxidative Stress Responses and Nutrient Starvation in MCHM TreatedG3 (Bethesda, Md.) · 2020Article
- Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.Journal of inherited metabolic disease · 2020Article
- Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae.Scientific reports · 2020Article
- Myo-inositol: its metabolism and potential implications for poultry nutrition-a review.Poultry science · 2020Review
- Impaired GCR1 transcription resulted in defective inositol levels, vacuolar structure and autophagy in Saccharomyces cerevisiae.Current genetics · 2019Article
- Crosstalk between Ras and inositol phosphate signaling revealed by lithium action on inositol monophosphatase in Schizophyllum commune.Advances in biological regulation · 2019Article
- Valproate inhibits glucose-stimulated insulin secretion in beta cells.Histochemistry and cell biology · 2018Article
- pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity.Microbial cell (Graz, Austria) · 2018Review
- pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal PathogenFrontiers in microbiology · 2017Article
- Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae.Scientific reports · 2016Article
- Combined Transcriptomics and Chemical-Genetics Reveal Molecular Mode of Action of Valproic acid, an Anticancer Molecule using Budding Yeast Model.Scientific reports · 2016Article
- The Inositol-3-Phosphate Synthase Biosynthetic Enzyme Has Distinct Catalytic and Metabolic Roles.Molecular and cellular biology · 2016Article
- Inositol depletion, GSK3 inhibition and bipolar disorder.Future neurology · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Depletion of inositol has profound effects on cell function and has been implicated in the therapeutic effects of drugs used to treat epilepsy and bipolar disorder. We have previously shown that the anticonvulsant drug valproate (VPA) depletes inositol by inhibiting myo-inositol-3-phosphate synthase, the enzyme that catalyzes the first and rate-limiting step of inositol biosynthesis. To elucidate the cellular consequences of inositol depletion, we screened the yeast deletion collection for VPA-sensitive mutants and identified mutants in vacuolar sorting and the vacuolar ATPase (V-ATPase). Inositol depletion caused by starvation of ino1Δ cells perturbed the vacuolar structure and decreased V-ATPase activity and proton pumping in isolated vacuolar vesicles. VPA compromised the dynamics of phosphatidylinositol 3,5-bisphosphate (PI3,5P2) and greatly reduced V-ATPase proton transport in inositol-deprived wild-type cells. Osmotic stress, known to increase PI3,5P2 levels, did not restore PI3,5P2 homeostasis nor did it induce vacuolar fragmentation in VPA-treated cells, suggesting that perturbation of the V-ATPase is a consequence of altered PI3,5P2 homeostasis under inositol-limiting conditions. This study is the first to demonstrate that inositol depletion caused by starvation of an inositol synthesis mutant or by the inositol-depleting drug VPA leads to perturbation of the V-ATPase.
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Registered trials
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