Disruption of iron homeostasis in Saccharomyces cerevisiae by high zinc levels:: a genome-wide study
Disruption of iron homeostasis in Saccharomyces cerevisiae by high zinc levels:: a genome-wide study
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DOI：
10.1111/j.1365-2958.2007.05807.x
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Arino, Joaquin
中科院分区：
文献类型：
--
作者：
Pagani, M. Ayelen;Casamayor, Antonio;Arino, Joaquin
锌是一种必需的金属，当过量时，可能对细胞有害。因此，这种阳离子的稳态机制必须进行微调。为了更好地理解酵母菌在过量锌面前的反应，我们筛选了一个系统性缺失突变体库，用于在6 mM锌存在下改变生长。89个突变体表现出增加的锌敏感性，包括许多基因参与液泡组装和blogenesis。有趣的是，一个突变体缺乏Aft 1转录因子，需要对铁饥饿的转录反应，被发现是高度敏感的锌。全基因组转录谱分析显示，暴露于5 mM ZnCl 2导致适当蛋白质折叠或靶向液泡和线粒体所需的许多分子伴侣以及参与应激反应（主要是氧化）、硫代谢和铁调节子的一些组分的基因的表达迅速增加。还研究了在不存在和存在锌过载的情况下缺乏Aft 1的影响。暴露于高锌产生活性氧和显着降低谷胱甘肽含量。有趣的是，锌过量导致细胞内铁含量下降，乌头酸酶和细胞色素c的活动在静止期的文化。这些发现表明，高锌水平可能会改变含铁硫蛋白的组装和/或功能，以及血红素组的生物合成，从而建立锌，铁和硫代谢之间的联系。
Zinc is an essential metal that, when in excess, can be deleterious to the cell. Therefore, homeostatic mechanisms for this cation must be finely tuned. To better understand the response of yeast in front of an excess of zinc, we screened a systematic deletion mutant library for altered growth in the presence of 6 mM zinc. Eighty-nine mutants exhibited increased zinc sensitivity, including many genes involved in vacuolar assembling and blogenesis. Interestingly, a mutant lacking the Aft1 transcription factor, required for the transcriptional response to iron starvation, was found to be highly sensitive to zinc. Genomewide transcriptional profiling revealed that exposure to 5 mM ZnCI2 results in rapid increase in the expression of numerous chaperones required for proper protein folding or targeting to vacuole and mitochondria, as well as genes involved in stress response (mainly oxidative), sulphur metabolism and some components of the iron regulon. The effect of the lack of Aft1 both in the absence and in the presence of zinc overload was also investigated. Exposure to high zinc generated reactive oxygen species and markedly decreased glutathione content. Interestingly, zinc excess results in decreased intracellular iron content and aconitase and cytochrome c activities in stationary-phase cultures. These findings suggest that high zinc levels may alter the assembly and/or function of iron-sulphur-containing proteins, as well as the biosynthesis of haem groups, thus establishing a link between zinc, iron and sulphur metabolism.