Loss of Ssql leads to mitochondrial dysfunction, activation of autophagy and cell cycle arrest due to iron overload triggered by mitochondrial iron-sulfur cluster assembly defects in Candida albicans

文献类型： 外文期刊

第一作者： Zhang, Dan

作者： Zhang, Dan;Yu, Qilin;Zhao, Qiang;Xiao, Chenpeng;Zhang, Kai;Jia, Chang;Chen, Sijia;Zhang, Bing;Li, Mingchun;Zhang, Biao;Dong, Yijie;Li, Mingchun

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关键词： Iron homeostasis;Mitochondrial dysfunction;autophagy;Cell cycle;Iron-sulfur cluster assembly;Candida albicans

期刊名称：INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY （ 影响因子：5.085； 五年影响因子：4.407 ）

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收录情况： SCI

摘要： Iron-sulfur clusters perform essential functions in enzymatic catalysis and homeostatic regulation. Here we for the first time identified Ssql as an essential component for iron-sulfur cluster assembly in Candida albicans. Ssql played an important role in cell growth. Shutting off SSQ1 led to accumulation of intracellular iron, especially in mitochondria, and disorder of intracellular iron regulation. In tetO-SSQ1, iron overloading triggered the oxidative damage of mitochondrial function. Surprisingly, disruption of SSQ1 activated autophagic pathway. The mitochondrial dysfunction was further aggravated when CCZ/ (which is essential for autophagy) and SSQ1 was simultaneously deleted, suggesting that autophagy played a critical role in maintenance of mitochondrial function in tetO-SSQ1. In addition, double deletion of SSQ1 and CCZI further elevated cellular iron levels in comparison with tetO-SSQ1, indicating that autophagy participated in maintenance of iron homeostasis. Furthermore, we found that loss of SSQ1 led to increasing protein expression of Rnrl and redistribution of Rnr2 from the nucleus to cytoplasm, and further resulted in cell cycle arrest. The results implied that cell cycle arrest was caused by activating the checkpoint pathway because of impairing the iron-sulfur cluster assembly in tetO-SSQ1. Shutting offSSQ1 led to a significant defect in filamentous development. Interestingly, the tetO-SSQ1ccz1 Delta/Delta growth was inhibited on hyphae-inducing solid media. Both tetO-SSQ1 and tetO-SSQ1ccz1 Delta/Delta exhibited extremely attenuated virulence, indicating that Ssql might provide a promising target for antifungal drugs development. In summary, our findings provide new insights into the understanding of iron-sulfur cluster assembly-related gene in C albicans. (C) 2017 Elsevier Ltd. All rights reserved.

分类号： Q5

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