Cells Adapt to Resist Fluoride through Metabolic Deactivation and Intracellular Acidification.
Cells Adapt to Resist Fluoride through Metabolic Deactivation and Intracellular Acidification.
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细胞通过代谢失活和细胞内酸化来抗氟化物。
DOI：
10.1021/acs.chemrestox.2c00222
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发表时间：
2022-11-21
影响因子：
4.1
通讯作者：
Cline, Gary
中科院分区：
文献类型：
--
作者：
Strobel, Scott A.;Johnston, Nichole R.;Cline, Gary
氟化物在环境中非常丰富。许多生物已经适应了针对高浓度氟的特定防御机制，包括表达能够从细胞中去除氟的蛋白质。然而，这些氟转运体并不是在所有的生物体中都被鉴定出来，即使是表达氟转运体的生物体，其耐受能力也因物种、个体甚至组织类型的不同而不同。这表明，替代因素影响氟化物耐受性。我们通过对缺乏氟化物输出子FEX的酿酒酵母进行无偏突变试验来筛选对氟化物毒性的适应性，FEX是氟化物抗性的主要机制。产生了80多个独立的氟化物硬化菌株，与原始菌株相比，氟化物耐受性提高了100到1200倍。对每个突变株的全基因组进行了测序，并与野生型进行了比较。氟化物强化菌株利用了一组单独授予氟化物耐受性的表型组合。这些包括细胞内酸化、细胞休眠、营养储存，以及让人联想到絮凝的共同行为。对氟化物抗性特别重要的是细胞内酸化，这有助于逆转氟化物的积累，并导致其以HF的形式从细胞中排泄出来，而不是氟化物特有的蛋白转运体的活性。这种转运机制也在野生型酵母中观察到，通过人工突变来降低细胞质pH。结果表明，酵母产生了一种无蛋白适应，可以去除细胞内的毒物。
Fluoride is highly abundant in the environment. Many organisms have adapted specific defense mechanisms against high concentrations of fluoride, including the expression of proteins capable of removing fluoride from cells. However, these fluoride transporters have not been identified in all organisms, and even organisms that express fluoride transporters vary in tolerance capabilities across species, individuals, and even tissue types. This suggests that alternative factors influence fluoride tolerance. We screened for adaptation against fluoride toxicity through an unbiased mutagenesis assay conducted on Saccharomyces cerevisiae lacking the fluoride exporter FEX, the primary mechanism of fluoride resistance. Over 80 independent fluoride-hardened strains were generated, with anywhere from 100- to 1200-fold increased fluoride tolerance compared to the original strain. The whole genome of each mutant strain was sequenced and compared to the wild type. The fluoride-hardened strains utilized a combination of phenotypes that individually conferred fluoride tolerance. These included intracellular acidification, cellular dormancy, nutrient storage, and a communal behavior reminiscent of flocculation. Of particular importance to fluoride resistance was intracellular acidification, which served to reverse the accumulation of fluoride and lead to its excretion from the cell as HF without the activity of a fluoride-specific protein transporter. This transport mechanism was also observed in wild-type yeast through a manual mutation to lower their cytoplasmic pH. The results demonstrate that the yeast developed a protein-free adaptation for removing an intracellular toxicant.
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影响因子：
3.7
作者：
Chen J;Tibroni N;Sauter D;Galaski J;Miura T;Alter G;Mueller B;Haller C;Walker BD;Kirchhoff F;Brumme ZL;Ueno T;Fackler OT
通讯作者：
Fackler OT
影响因子：
4.6
作者：
Liu X;Tian J;Liu L;Zhu T;Yu X;Chu X;Yao B;Wu N;Fan Y
通讯作者：
Fan Y
影响因子：
4.3
作者：
Ling-Fei He;Jian-Gang Chen
通讯作者：
Jian-Gang Chen
DOI：
10.1073/pnas.1310439110
发表时间：
2013-11-19
影响因子：
11.1
作者：
Li, Sanshu;Smith, Kathryn D.;Strobel, Scott A.
通讯作者：
Strobel, Scott A.
影响因子：
4.1
作者：
Johnston, Nichole R.;Strobel, Scott A.
通讯作者：
Strobel, Scott A.