MTM1 plays an important role in the regulation of zinc tolerance in Saccharomyces cerevisiae
MTM1 plays an important role in the regulation of zinc tolerance in Saccharomyces cerevisiae
复制标题
DOI：
10.1016/j.jtemb.2021.126759
复制
发表时间：
2021-04-16
影响因子：
3.5
通讯作者：
Wu, Xiaobin
中科院分区：
文献类型：
--
作者：
Bian, Jiang;Wang, Lingyun;Wu, Xiaobin
背景：锌的获取和分布支持许多生物过程。锌代谢的分子调控因素很多，但尚未完全阐明。基本步骤：通过过量锌培养酵母，获得自发突变体，然后进行全基因组DNA测序，利用生物信息学方法寻找锌代谢相关基因。通过金属组学和分子生物学方法，其特征在于一个确定的突变体。主要发现：在这里，我们报道了MTM1基因敲除细胞显示更强的锌耐受性比野生型细胞在SC培养基上暴露于过量的锌。与野生型细胞相比，在过量锌条件下，MTM1 Delta细胞的锌积累显著降低，这是由于MTM1缺失降低了锌摄取。mtm1 Delta细胞中ZRCI mRNA水平显著高于野生型菌株，导致mtin14细胞中液泡锌积累增加。mtm1 Delta细胞中ZRTI和ZAPI的mRNA水平降低，导致锌摄取减少。zrc1 Δ mtm1 Δ双敲除菌株表现出Zn敏感性。MTM 1敲除并没有通过影响活性氧水平介导的效应来提供对过量锌的抵抗力。超氧化物歧化酶2（Sod2p）的活性在mtm1三角洲细胞严重受损，并没有恢复，通过锌补充。结论：MTM1基因通过改变锌的吸收和分布，在调节酵母细胞锌稳态中发挥重要作用。这一发现为更好地理解液泡和线粒体之间与锌代谢有关的生化通讯提供了新的见解。
Background: Acquisition and distribution of zinc supports a number of biological processes. Various molecular factors are involved in zinc metabolism but not fully explored.Basic procedures: Spontaneous mutants were generated in yeast with excess zinc culture followed by whole genome DNA sequencing to discover zinc metabolism related genes by bioinformatics. An identified mutant was characterized through metallomic and molecular biology methods.Main findings: Here we reported that MTM1 knockout cells displayed much stronger zinc tolerance than wild type cells on SC medium when exposed to excess zinc. Zn accumulation of mtm1 Delta cells was dramatically decreased compared to wild type cells under excessive zinc condition due to MTM1 deletion reduced zinc uptake. ZRCI mRNA level of mtm1 Delta cells was significantly higher than that in the wild-type strain leading to increased vacuolar zinc accumulations in mtin14 cells. The mRNA levels of ZRTI and ZAPI decreased in mtm1 Delta cells contributing to less Zn uptake. The zrc1 Delta mtm1 Delta double knockout strain exhibited Zn sensitivity. MTM1 knockout did not afford resistance to excess zinc through an effect mediated through an influence on levels of ROS. Superoxide dismutase 2 (Sod2p) activity in mtm1 Delta cells was severely impaired and not restored through Zn supplementation. Meanwhile, additional Zn showed no significant effect on the localization and expression of Mtm1p.Principal conclusions: Our study reveals the MTM1 gene plays an important role in the regulation of zinc homeostasis in yeast cells via changing zinc uptake and distribution. This discovery provides new insights for better understanding biochemical communication between vacuole and mitochondrial in relation to zinc-metabolism.