Expansion, functional diversification, and gene fusion events in the Ato protein family.

The human commensal, Candida albicans, adapts to glucose-limited niches by utilizing alternative carbon sources such as carboxylates. Saccharomyces cerevisiae can assimilate monocarboxylates via Ato1 (Ady2), a member of the Acetate Uptake Transporter (AceTr) family. In C. albicans, this Ato family has expanded significantly to 10 members (Ato1-Ato10), most with unknown functions. Therefore, we investigated the roles of C. albicans Ato proteins in carboxylate utilization. Functional diversification of C. albicans Atos (CaAtos), suggested by in silico analyses of their AceTr motifs, pore radii, and substrate-binding sites, was confirmed by experimental dissection of their carboxylate transport capacities, revealing CaAto1 as the major acetate transporter, driven by the proton motive force. CaAto1-3 and CaAto6 showed carboxylate-dependent expression and plasma membrane localization. Furthermore, CaATO1 deletion resulted in endoplasmic reticulum (ER) retention of CaAto2 and loss of CaAto3 expression, indicating a central regulatory role for CaAto1. Our analyses reveal further evolutionary diversification of the Ato family in vertebrates.