Manganese is a crucial cofactor for a wide range of enzymes in many living cells. However, excessive manganese can induce cellular toxicity by affecting a number of metabolic reactions and even cause severe neurological diseases in humans. To understand manganese homeostasis fully, a genome-scale screen was performed using the homozygous diploid yeast deletion mutant library. We identified 152 manganese-sensitive and 13 manganese-tolerant gene deletion mutations. We found that 62 of the manganese-sensitive mutants (40% of the total) accumulated higher intracellular manganese compared to wild type. Our results also reinforced the genetic functional link between manganese and calcium, and the addition of 100 mM CaCl2 confirmed that the manganese sensitivities of 103 (67.8 % of the total) strains could be inhibited by calcium. Finally, this study demonstrated that there might be some significant interactions between manganese and calcium regulated by the calcium/calcineurin signaling pathway through the P-type Ca2+- and Mn2+-transporting ATPase, Pmr1. Taken together, our current findings would provide new insights into the molecular causes of manganese toxicity in yeast cells.
Keywords: Pmr1; Saccharomyces cerevisiae; calcium signaling pathway; manganese homeostasis.