Cdc1 and the vacuole coordinately regulate Mn2+ homeostasis in the yeast Saccharomyces cerevisiae

Abstract

The yeast CDC1 gene encodes an essential protein that has been implicated in the regulation of cytosolic [Mn2+]. To identify factors that impinge upon Cdc1 or the Cdc1-dependent process, we isolated second-site suppressors of the conditional cdc1-1(Ts) growth defect. Recessive suppressor define 15 COS (Cdc One Suppressor) genes. Seven of the fifteen COS genes are required for biogenesis of the vacuole, an organelle known to sequester intracellular Mn2+. An eighth gene, COS16, encodes a vacuolar membrane protein that seems to be involved in Mn2+ homeostasis. These results suggest mutations that block vacuolar Mn2+ sequestration compensate for defects in Cdc1 function. Interestingly, Cdc1 is dispensable in a cos16Δ deletion strain, and a cdc1Δ cos16Δ double mutant exhibits robust growth on medium supplemented with Mn2+. Thus, the single, essential function of Cdc1 is to regulate intracellular, probably cytosolic, Mn2+.