Identification and functional characterization of mitochondrial carrier Mrs4 in Candida albicans

Abstract

Iron is an essential nutrient required for the growth and metabolism in Candida albicans. Here, we for the first time identified Mrs4 as a new member of mitochondrial carrier family in C. albicans. Our experiments revealed that C. albicans Mrs4 (CaMrs4) is localized to the mitochondria and required for mitochondrial morphology. We found that CaMrs4 is required for cell growth, and the mrs4Δ/Δ mutant showed a more severe growth defect in iron deficiency. Deletion of MRS4 affected cellular iron content by altering the expression of iron regulon genes in C. albicans, such as AFT2, SMF3, FTR1 and ISU1. Candida albicans Aft2 factor functions as a negative regulator of MRS4 expression through the CACCC Aft-type sequence in a gene dose-dependent fashion. In addition, the mrs4Δ/Δ mutant exhibited hypersensitivity to oxidants and most metal ions, but decreased sensitivity to cobalt. Exogenous iron could suppress the sensitivity of the mrs4Δ/Δ mutant to oxidants and most metal ions, suggesting that the role of CaMrs4 is partially mediated by iron availability. Furthermore, deletion of MRS4 resulted in delayed filamentation under tested conditions. Taken together, these findings characterize a new mitochondrial carrier and provide a novel insight into the role of CaMrs4 in mitochondrial function.