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暴露于技术关键元素钇的全球缺失基因组图谱。

Global Deletome Profile of Exposed to the Technology-Critical Element Yttrium.

作者信息

Grosjean Nicolas, Gross Elisabeth M, Le Jean Marie, Blaudez Damien

机构信息

Université de Lorraine, CNRS, LIEC, Nancy, France.

Université de Lorraine, CNRS, LIEC, Metz, France.

出版信息

Front Microbiol. 2018 Sep 4;9:2005. doi: 10.3389/fmicb.2018.02005. eCollection 2018.

Abstract

The emergence of the technology-critical-element yttrium as a contaminant in the environment raises concern regarding its toxicological impact on living organisms. The molecular mechanisms underlying yttrium toxicity must be delineated. We considered the genomic phenotyping of a mutant collection of to be of particular interest to decipher key cellular pathways involved either in yttrium toxicity or detoxification mechanisms. Among the 4733 mutants exposed to yttrium, 333 exhibited modified growth, of which 56 were sensitive and 277 were resistant. Several functions involved in yttrium toxicity mitigation emerged, primarily vacuolar acidification and retrograde transport. Conversely, functional categories overrepresented in the yttrium toxicity response included cytoskeleton organization and endocytosis, protein transport and vesicle trafficking, lipid metabolism, as well as signaling pathways. Comparison with similar studies carried out using other metals and stressors showed a response pattern similar to nickel stress. One third of the identified mutants highlighted peculiar cellular effects triggered by yttrium, specifically those affecting the pheromone-dependent signaling pathway or sphingolipid metabolic processes. Taken together, these data emphasize the role of the plasma membrane as a hotspot for yttrium toxicity. The up-to-now lack of data concerning yttrium toxicity at the cellular and molecular levels makes this pioneer study using the model an excellent first basis for the assessment of yttrium toxicity toward eukaryotes.

摘要

作为环境污染物的技术关键元素钇的出现引发了人们对其对生物有机体毒理学影响的担忧。必须阐明钇毒性背后的分子机制。我们认为对一个突变体库进行基因组表型分析对于解读参与钇毒性或解毒机制的关键细胞途径特别有意义。在4733个暴露于钇的突变体中,333个表现出生长改变,其中56个敏感,277个抗性。出现了几个与减轻钇毒性有关的功能,主要是液泡酸化和逆向转运。相反,在钇毒性反应中过度代表的功能类别包括细胞骨架组织和内吞作用、蛋白质运输和囊泡运输、脂质代谢以及信号通路。与使用其他金属和应激源进行的类似研究相比,显示出与镍应激相似的反应模式。三分之一的已鉴定突变体突出了钇引发的特殊细胞效应,特别是那些影响信息素依赖性信号通路或鞘脂代谢过程的效应。综上所述,这些数据强调了质膜作为钇毒性热点的作用。目前在细胞和分子水平上缺乏关于钇毒性的数据,使得这项使用该模型的开创性研究成为评估钇对真核生物毒性的一个极好开端。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30f3/6131306/64630c97a841/fmicb-09-02005-g001.jpg

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