The Transcriptional Activator Imp2p Maintains Ion Homeostasis in Saccharomyces cerevisiae

Yeast cells deficient in the transcriptional activator Imp2p are viable, but display marked hypersensitivity to a variety of oxidative agents. We now report that imp2 null mutants are also extremely sensitive to elevated levels of the monovalent ions, Na+ and Li+, as well as to the divalent ions Ca2+, Mn2+, Zn2+, and Cu2+, but not to Cd2+, Mg2+, Co2+, Ni2+, and Fe2+, as compared to the parent strain. We next searched for multicopy suppressor genes that would allow the imp2Δ mutant to grow under high salt conditions. Two genes that independently restored normal salt-resistance to the imp2Δ mutant, ENA1 and HAL3, were isolated. ENA1 encodes a P-type ion pump involved in monovalent ion efflux from the cell, while HAL3 encodes a protein required for activating the expression of Ena1p. Neither ENA1 nor HAL3 gene expression was positively regulated by Imp2p. Moreover, the imp2 ena1 double mutant was exquisitely sensitive to Na+/Li+ cations, as compared to either single mutant, implying that Imp2p mediates Na+/Li+ cation homeostasis independently of Ena1p.