ArticlePloS one2011
Genome-wide analysis reveals the vacuolar pH-stat of Saccharomyces cerevisiae.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 89 citations in OpenAlex.
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- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
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- Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann-Pick Type C1.International journal of molecular sciences · 2023Article
- Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.Reviews of physiology, biochemistry and pharmacology · 2023Article
- The phospholipid flippase ATP8B1 is required for lysosomal fusion in macrophages.Cell biochemistry and function · 2022Article
- Comparative chemical genomic profiling across plant-based hydrolysate toxins reveals widespread antagonism in fitness contributions.FEMS yeast research · 2022Article
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- Recent Advances in Electrochemical Biosensors: Applications, Challenges, and Future Scope.Biosensors · 2021Review
- The Role of Sch9 and the V-ATPase in the Adaptation Response to Acetic Acid and the Consequences for Growth and Chronological Lifespan.Microorganisms · 2021Article
- Plasma Membrane Protein Nce102 Modulates Morphology and Function of the Yeast Vacuole.Biomolecules · 2020Article
- Sulforaphane alters the acidification of the yeast vacuole.Microbial cell (Graz, Austria) · 2020Article
- A new pH sensor localized in the Golgi apparatus of Saccharomyces cerevisiae reveals unexpected roles of Vph1p and Stv1p isoforms.Scientific reports · 2020Article
- Conserved mechanism of phospholipid substrate recognition by the P4-ATPase Neo1 from Saccharomyces cerevisiae.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Article
- Genome-Wide Identification of Genes Involved in General Acid Stress and Fluoride Toxicity inFrontiers in microbiology · 2020Article
- Regulation of V-ATPase Activity and Organelle pH by Phosphatidylinositol Phosphate Lipids.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Protons, the smallest and most ubiquitous of ions, are central to physiological processes. Transmembrane proton gradients drive ATP synthesis, metabolite transport, receptor recycling and vesicle trafficking, while compartmental pH controls enzyme function. Despite this fundamental importance, the mechanisms underlying pH homeostasis are not entirely accounted for in any organelle or organism. We undertook a genome-wide survey of vacuole pH (pH(v)) in 4,606 single-gene deletion mutants of Saccharomyces cerevisiae under control, acid and alkali stress conditions to reveal the vacuolar pH-stat. Median pH(v) (5.27±0.13) was resistant to acid stress (5.28±0.14) but shifted significantly in response to alkali stress (5.83±0.13). Of 107 mutants that displayed aberrant pH(v) under more than one external pH condition, functional categories of transporters, membrane biogenesis and trafficking machinery were significantly enriched. Phospholipid flippases, encoded by the family of P4-type ATPases, emerged as pH regulators, as did the yeast ortholog of Niemann Pick Type C protein, implicated in sterol trafficking. An independent genetic screen revealed that correction of pH(v) dysregulation in a neo1(ts) mutant restored viability whereas cholesterol accumulation in human NPC1(-/-) fibroblasts diminished upon treatment with a proton ionophore. Furthermore, while it is established that lumenal pH affects trafficking, this study revealed a reciprocal link with many mutants defective in anterograde pathways being hyperacidic and retrograde pathway mutants with alkaline vacuoles. In these and other examples, pH perturbations emerge as a hitherto unrecognized phenotype that may contribute to the cellular basis of disease and offer potential therapeutic intervention through pH modulation.
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