Pathogenic fungi must appropriately sense the host availability of essential metals such as Fe. In Candida albicans and other yeasts, sensing of Fe involves mitochondrial Fe‐S clusters. Yeast mutants for Fe‐S cluster assembly sense Fe limitation even when Fe is abundant and hyperaccumulate Fe. We observe this same disrupted Fe sensing with C. albicans mutants of SMF11, a NRAMP transporter of divalent metals. Mutants of smf11 hyperaccumulate both Mn and Fe and the elevated Mn is secondary to Fe overload. As with Fe‐S biogenesis mutants, smf11∆/∆ mutants show upregulation of ferric reductases that are normally repressed under high Fe, and Fe import is activated. However, unlike Fe‐S biogenesis mutants, smf11∆/∆ mutants show no defects in mitochondrial Fe‐S enzymes. Intriguingly, this exact condition of disrupted Fe sensing without inhibiting Fe‐S clusters occurs with C. albicans fre1∆/∆ mutants encoding a ferric reductase. Mutants of fre1 and smf11 display similar perturbations in the cell wall, in filamentation and in the ROS burst of morphogenesis, a Fe‐dependent process. As with FRE1, SMF11 is important for virulence in a mouse model for disseminated candidiasis. We propose a model in which FRE1 and SMF11 operate outside the mitochondrial Fe‐S pathway to donate ferrous Fe for Fe sensing.

中文翻译：

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金属转运蛋白 SMF11 和铁还原酶 FRE1 在白色念珠菌铁稳态中的融合作用


病原真菌必须适当地感知宿主对 Fe 等必需金属的可用性。在白色念珠菌和其他酵母中，Fe 的感应涉及线粒体 Fe-S 簇。Fe-S 簇组装的酵母突变体即使 Fe 丰富且 Fe 过度积累，也能感知 Fe 限制。我们用 SMF11 的白色念珠菌突变体观察到同样的 Fe 感应中断，SMF11 是二价金属的 NRAMP 转运蛋白。smf11 的突变体在 Mn 和 Fe 上都过度积累，并且升高的 Mn 继发于 Fe 超负荷。与 Fe-S 生物发生突变体一样，smf11∆/∆ 突变体表现出通常在高 Fe 下被抑制的铁还原酶的上调，并且 Fe 输入被激活。然而，与 Fe-S 生物发生突变体不同，smf11∆/∆ 突变体在线粒体 Fe-S 酶中没有缺陷。有趣的是，这种 Fe 感应被破坏而不抑制 Fe-S 簇的确切情况发生在编码铁还原酶的白色念珠菌 fre1∆/∆ 突变体中。fre1 和 smf11 的突变体在细胞壁、细丝化和形态发生的 ROS 爆发（一种 Fe 依赖性过程）中表现出类似的扰动。与 FRE1 一样，SMF11 对于播散性念珠菌病小鼠模型中的毒力很重要。我们提出了一个模型，其中 FRE1 和 SMF11 在线粒体 Fe-S 通路之外运行，以提供亚铁 Fe 用于 Fe 感应。