Genome-wide analysis of manganese homeostasis in Saccharomyces cerevisiae

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.