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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin
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A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin

机译：酿酒酵母的全基因组筛选揭示了线粒体在单端孢霉菌真菌毒素毒性中的关键作用

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摘要

Trichothecene mycotoxins synthesized by Fusarium species are potent inhibitors of eukaryotic translation. They are encountered in both the environment and in food, posing a threat to human and animal health. They have diverse roles in the cell that are not limited to the inhibition of protein synthesis. To understand the trichothecene mechanism of action, we screened the yeast knockout library to identify genes whose deletion confers resistance to trichothecin (Tcin). The largest group of resistant strains affected mitochondrial function, suggesting a role for fully active mitochondria in trichothecene toxicity. Tcin inhibited mitochondrial translation in the wild-type strain to a greater extent than in the most resistant strains, implicating mitochondrial translation as a previously unrecognized site of action. The Tcin-resistant strains were cross-resistant to anisomycin and chloramphenicol, suggesting that Tcin targets the peptidyltransferase center of mitochondrial ribosomes. Tcin-induced cell death was partially rescued by mutants that regulate mitochondrial fusion and maintenance of the tubular morphology of mitochondria. Treatment of yeast cells with Tcin led to the fragmentation of the tubular mitochondrial network, supporting a role for Tcin in disruption of mitochondrial membrane morphology. These results provide genome-wide insight into the mode of action of trichothecene mycotoxins and uncover a critical role for mitochondrial translation and membrane maintenance in their toxicity.
机译：镰刀菌属物种合成的单端孢霉菌真菌毒素是真核翻译的有效抑制剂。它们在环境和食物中都遇到，对人类和动物健康构成威胁。它们在细胞中具有多种作用，而不仅限于抑制蛋白质合成。为了了解天花粉蛋白的作用机理，我们筛选了酵母基因敲除文库，以鉴定其缺失赋予对天花粉蛋白（Tcin）的抗性的基因。最大的一类耐药菌株影响线粒体功能，提示线粒体完全活性的线粒体在天花粉毒性中起作用。与最具抗药性的菌株相比，Tcin在野生型菌株中抑制线粒体翻译的程度更大，暗示线粒体翻译是以前无法识别的作用位点。耐Tcin的菌株对茴香霉素和氯霉素具有交叉耐药性，表明Tcin靶向线粒体核糖体的肽基转移酶中心。调节线粒体融合并维持线粒体管状形态的突变体可部分挽救Tcin诱导的细胞死亡。用Tcin处理酵母细胞导致管状线粒体网络破裂，从而支持Tcin在破坏线粒体膜形态中的作用。这些结果提供了全基因组深入了解天花粉真菌毒素的作用方式，并揭示了线粒体翻译和膜维持毒性的关键作用。

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    John E. McLaughlin; Mohamed Anwar Bin-Umer; Andrew Tortora; Natasha Mendez; Susan McCormick; Nilgun E. Turner;

  • 作者单位

    Biotechnology Center for Agriculture and the Environment and the Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, MJ, 08901-8520;

    Biotechnology Center for Agriculture and the Environment and the Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, MJ, 08901-8520;

    Biotechnology Center for Agriculture and the Environment and the Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, MJ, 08901-8520;

    Biotechnology Center for Agriculture and the Environment and the Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, MJ, 08901-8520;

    Mycotoxin Research Unit, National Center for Agricultural Utilization Research, United States Department of Agriculture, Agricultural Research Service, Peoria, IL, 61604;

    Biotechnology Center for Agriculture and the Environment and the Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, MJ, 08901-8520;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    Fusarium head blight; ribosome; translation; deoxynivalenol; mycotoxin;

    机译：镰刀菌病核糖体翻译;脱氧雪腐烯醇;霉菌毒素;

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