Vacuolar functions determine the mode of cell death.
The yeast vacuole plays a crucial role in cell homeostasis including pH regulation and degradation of proteins and organelles. Class C VPS genes code for proteins essential for vacuolar and endosomal vesicle fusion, their deletion results in the absence of a detectable vacuole. We found that single gene deletions of class C VPS genes result in a drastically enhanced sensitivity to treatment with acetic acid whereas sensitivity towards H2O2 remains largely unaffected. Interestingly acetic acid treatment known as an established inducer of yeast apoptosis leads to necrosis in class C VPS deletion strains. Their intracellular pH drops from 6.7 to 5.5 after acetic acid treatment, while in wild type the pH drops to just 6.3. When the intracellular pH in wild type is lowered below pH 5.5 using a higher concentration of acetic acid, the survival rate is similarly low as in the class C VPS mutants, however, the death phenotype is predominantly apoptotic. Hence, the vacuole not only prevents acetic acid induced cell death by buffering the cytosolic pH, but it also has a proapoptotic function.
Schauer
Alexandra
A
Institute of Molecular Biosciences, University of Graz, Humboldtstrabetae 50, 8010 Graz, Austria.
Knauer
Heide
H
Ruckenstuhl
Christoph
C
Fussi
Heike
H
Durchschlag
Michael
M
Potocnik
Ulrike
U
Fröhlich
Kai-Uwe
KU
D017209:Apoptosis; D006863:Hydrogen-Ion Concentration; D009336:Necrosis; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins