Kim H~Cunningham KW, 2012

Pubmed ID 22511765
Title Vacuolar H+-ATPase (V-ATPase) promotes vacuolar membrane permeabilization and nonapoptotic death in stressed yeast.
Authors Hyemin Kim, Adam Kim, Kyle W Cunningham
Abstract Stress in the endoplasmic reticulum caused by tunicamycin, dithiothreitol, and azole-class antifungal drugs can induce nonapoptotic cell death in yeasts that can be blocked by the action of calcineurin (Cn), a Ca(2+)-dependent serine/threonine protein phosphatase. To identify additional factors that regulate nonapoptotic cell death in yeast, a collection of gene knock-out mutants was screened for mutants exhibiting altered survival rates. The screen revealed an endocytic protein (Ede1) that can function upstream of Ca(2+)/calmodulin-dependent protein kinase 2 (Cmk2) to suppress cell death in parallel to Cn. The screen also revealed the vacuolar H(+)-ATPase (V-ATPase), which acidifies the lysosome-like vacuole. The V-ATPase performed its death-promoting functions very soon after imposition of the stress and was not required for later stages of the cell death program. Cn did not inhibit V-ATPase activities but did block vacuole membrane permeabilization (VMP), which occurred at late stages of the cell death program. All of the other nondying mutants identified in the screens blocked steps before VMP. These findings suggest that VMP is the lethal event in dying yeast cells and that fungi may employ a mechanism of cell death similar to the necrosis-like cell death of degenerating neurons.
Citation J. Biol. Chem. 2012; 287:19029-39
Notes 1,4-dithiothreitol (4 mM) +/- tacrolimus (1 ug/ml) was also tested for a smaller subset of 659 mutants (not included here).

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Kim H~Cunningham KW, 2012 cell death (frequency of dead cells) tunicamycin [2.5 ug/ml] hap a 4,785 Quantitative
Kim H~Cunningham KW, 2012 cell death (frequency of dead cells) tacrolimus (anhydrous) [1 ug/ml], tunicamycin [2.5 ug/ml] hap a 4,785 Quantitative

Curation history

Data

March 11, 2013 Loaded.

Tested strains

March 11, 2013 Loaded.