Fission yeast cells deficient in siderophore biosynthesis require Str2 for ferrichrome-dependent growth

Ferrichrome (Fc) acquisition in <i>Schizosaccharomyces pombe</i> is mediated by the cell-surface siderophore-iron transporter Str1. Here, we report that Str2, a protein homologous to Str1, localizes to the vacuolar membrane. Like Str1, Str2 expression is transcriptionally regulated in response to changes in iron concentrations. Both the <i>str2⁺</i> and <i>str1⁺</i> genes are induced under low-iron conditions and are repressed by the iron-responsive GATA-type transcription factor Fep1 when iron is abundant. Under high-iron conditions, chromatin immunoprecipitation (ChIP) assays reveal that TAP-Fep1 occupies the <i>str2⁺</i> and <i>str1⁺</i> promoters. Isolated vacuoles from <i>str2Δ fep1Δ</i> cells expressing GFP-tagged Str2 exhibit iron accumulation in vacuoles upon exposure to exogenous holo-Fc. <i>sib1Δ sib2Δ</i> cells deficient in Fc biosynthesis and lacking the <i>str2⁺</i> gene (<i>str2Δ</i>) are unable to grow in the presence of exogenous Fc as a sole source of iron. Further analysis identified that conserved amino acids Tyr⁵³⁹ and Tyr⁵⁵³ in the last predicted loop of Str2 are required for supporting Fc-dependent growth of a <i>sib1Δ sib2Δ</i> mutant strain. Collectively, these findings indicate that the vacuolar Str2 protein plays a role in the consumption of Fc as an iron source, while also revealing the involvement of the vacuole in iron release from exogenous Fc after its assimilation.