Brett CL~Rao R, 2011

Pubmed ID 21423800
Title Genome-wide analysis reveals the vacuolar pH-stat of Saccharomyces cerevisiae.
Authors Christopher L Brett, Laura Kallay, Zhaolin Hua, Richard Green, Anthony Chyou, Yongqiang Zhang, Todd R Graham, Mark Donowitz, Rajini Rao
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.
Citation PLoS ONE 2011; 6:e17619

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Brett CL~Rao R, 2011 vacuolar pH pH [2.7] hap alpha 4,500 Quantitative
Brett CL~Rao R, 2011 vacuolar pH pH [4.0] hap alpha 4,561 Quantitative
Brett CL~Rao R, 2011 vacuolar pH pH [7.0] hap alpha 4,548 Quantitative
Brett CL~Rao R, 2011 growth (culture turbidity) pH [2.7] hap alpha 4,385 Quantitative
Brett CL~Rao R, 2011 growth (culture turbidity) pH [4.0] hap alpha 4,531 Quantitative
Brett CL~Rao R, 2011 growth (culture turbidity) pH [7.0] hap alpha 4,506 Quantitative

Curation history

Data

July 18, 2013 Loaded.

Tested strains

July 18, 2013 Loaded.