Influence of the members of ras/pka signal transduction pathway on the yeast Saccharomyces cerevisiae cell death induced by natural acidification of the medium

Abstract

Constantly changing environment is the major factor controlling the growth and development of the microorganisms. For quick generation of the cell response, information about changes in the cell environment is rapidly transmitted to the inner molecules of the cell. During the course of evolution the cells have developed signaling systems that are able to combine extracellular signals with the inner processes, as transcription, translation etc. One of the universal signaling systems is Ras/PKA signal transduction pathway. This system helps cells recognize the nutrient sources present in the growth medium.Environmental pH is one of the main factors influencing the growth, physiology and differentiation of yeast. In Saccharomyces cerevisiae, response to pH is determined by the RIM101 pathway. Recently, it was shown, that Ras/PKA signal transduction pathway regulates cell aging as response to environmental pH. Many aging and apoptosis features are conserved between yeast and multicellular microorganisms, and this makes them perfect model organisms. Yeasts are also suitable also for acidosis related disease studies. Evaluation of the cell growth and medium acidification of isogenic strains containing mutation in the members of Ras/PKA signal transduction pathway was performed. Mutations in these genes cause changes in metabolic activity of the cell.Members of the Ras/PKA signal transduction pathway participate in regulation of cell viability and lifespan during the natural gradual acidification of the medium and under acidic stress conditions. In this process RAS genes are acting as negative regulators. PDE1 gene is also negative regulator of the cell viability in these conditions. It was determined, that buffering of the medium increases lifespan significantly. Analysis of the cell death type showed that hyperactivation of the Ras/PKA signal transduction pathway caused by Ras2Val19 mutation induces apoptosis in yeast cells. Vice versa, downregulation of the pathway by deletion of RAS1 and RAS2 genes act as necrosis inducer. Activity of the phosphodiesterase 2 is related to the termination of the apoptosis in yeast cells and inactivation of the both phosphodiesterase genes induces necrosis in yeast cells. Buffering of the medium causes decreased cell mortality with apoptosis related markers. It was proved; that members of Ras/PKA signal transduction pathway regulate cell metabolism, viability, aging and death type during natural acidification of the environment and under acidic stress conditions