title: Ras/PKA signal transduction pathway participates in the regulation of Saccharomyces cerevisiae cell apoptosis in an acidic environment.
abstract: The acidification of the medium is observed during yeast cell growth. This process contributes to the emission of organic acids, mainly acetic acid. Acetic acid is known as the inducer of apoptosis in the yeast Saccharomyces cerevisiae. In this study, we showed that hydrochloric acid can also induce apoptosis in yeast cells, and the apoptotic phenotype triggered by treating yeast cells with hydrochloric acid is modulated by the Ras/PKA pathway. The Ras/PKA pathway is highly conserved between all eukaryotic organisms, as well as cell processes that are related to apoptosis and aging. In this research, we demonstrated that the activation of the Ras/PKA pathway by insertion of Ras2(Val19) allele or deletion of PDE2 gene increases cell death, displaying the markers of apoptosis in an acidic environment. Downregulation of the pathway by deletion of RAS2, RAS1, PDE1, and insertion of the Ha-ras gene increases the cell viability and diminishes cell death with the apoptotic phenotypes. The deletion of PDE1 gene and double deletion of both phosphodiesterase genes prevent the induction of apoptosis in the cells. Modulations in the Ras/PKA pathway affect cell viability and apoptosis during natural gradual acidification of the medium as well as in acid stress conditions.
authors.affiliation: Department of Microbiology and Biotechnology, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
authors.forename: Eglė
authors.initials: E
authors.lastname: Lastauskienė
authors.forename: Auksė
authors.initials: A
authors.lastname: Zinkevičienė
authors.forename: Donaldas
authors.initials: D
authors.lastname: Čitavičius
mesh_terms: D017209:Apoptosis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D018631:ras Proteins
keywords: Hydrochloric acid; Ras/PKA; apoptosis; medium acidification; signal transduction; yeast