Function and Regulation of the Saccharomyces cerevisiae ENA Sodium ATPase System

Despite the fact that sodium ions are necessary to assist in the function of specific macromolecules (65), for most eukaryotic cells an elevated intracellular concentration of sodium ions is deleterious, probably because they interfere with the correct functioning of certain cellular targets (83). Because of the abundance of sodium ions in natural environments, yeasts and many other eukaryotic cells have developed mechanisms to maintain a relatively low intracellular concentration of this cation and/or to sequester it into organelles. The yeast Saccharomyces cerevisiae is a model organism used very often for cation tolerance studies. In this organism, maintenance of intracellular low sodium when sodium is present in excess in the external medium relies heavily on the capacity to extrude the cation. This is achieved by two main extrusion mechanisms. The first one is an H/Na antiporter encoded by the NHA1 gene, which is able to extrude Na ,L i, and even K cations by exchange with protons, gaining biological significance at rather acidic external pHs (8, 73). The second is based on a P-type ATPase pump encoded by the ENA system, which is the subject of this review. Although both mechanisms are complementary, comparison of the phenotypes of strains lacking functional antiporter or ATPase genes suggests that under standard growth conditions, the ENA system is the major determinant for sodium detoxification. The importance of this efflux system is highlighted by the observation that it seems to be present in all fungi as well as in certain nonflowering plants, such as bryophytes. In addition, active research with S. cerevisiae has revealed a complex and sophisticated system of transcriptional regulation in response to specific environmental changes, which is the major issue of this review.