Genetic interactions among the Arl1 GTPase and intracellular Na(+) /H(+) antiporters in pH homeostasis and cation detoxification.

The roles of intracellular GTPase Arl1 and organellar cation/H(+) antiporters (Kha1 and Nhx1) in Saccharomyces cerevisiae tolerance to various stress factors were investigated and interesting new phenotypes of strains devoid of these proteins were found. The role of Arl1 GTPase in their tolerance to various cations is not caused by an altered plasma-membrane potential. Besides the known sensitivity of arl1 mutants to high temperature, we discovered their sensitivity to low temperature. We found for the first time that in the absence of Arl1p, Kha1p increases potassium, sodium and lithium tolerance, and can thus be categorized as an antiporter with broad substrate specificity. Kha1p also participates in the detoxification of undesired chemical compounds, pH regulation and growth at nonoptimal temperatures. Cells with the combined deletions of all three genes have considerable difficulty growing under nonoptimal conditions. We conclude that Arl1p, Kha1p and Nhx1p collaborate in survival strategies at nonoptimal pH, temperatures and cation concentrations, but work independent of each other.