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首页> 外文期刊>Biology Open >Disruption of a cystine transporter downregulates expression of genes involved in sulfur regulation and cellular respiration
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Disruption of a cystine transporter downregulates expression of genes involved in sulfur regulation and cellular respiration

机译：胱氨酸转运蛋白的破坏下调了参与硫调节和细胞呼吸的基因的表达

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Cystine and cysteine are important molecules for pathways such as redox signaling and regulation, and thus identifying cellular deficits upon deletion of the?Saccharomyces cerevisiae?cystine transporter Ers1p allows for a further understanding of cystine homeostasis. Previous complementation studies using the human ortholog suggest yeast Ers1p is a cystine transporter. Human?CTNS?encodes the protein Cystinosin, a cystine transporter that is embedded in the lysosomal membrane and facilitates the export of cystine from the lysosome. When?CTNS?is mutated, cystine transport is disrupted, leading to cystine accumulation, the diagnostic hallmark of the lysosomal storage disorder cystinosis. Here, we provide biochemical evidence for Ers1p-dependent cystine transport. However, the accumulation of intracellular cystine is not observed when the?ERS1?gene is deleted from?ers1-Δ yeast, supporting the existence of modifier genes that provide a mechanism in?ers1-Δ yeast that prevents or corrects cystine accumulation. Upon comparison of the transcriptomes of isogenic?ERS1+?and?ers1-Δ strains of?S. cerevisiae?by DNA microarray followed by targeted qPCR, sixteen genes were identified as being differentially expressed between the two genotypes. Genes that encode proteins functioning in sulfur regulation, cellular respiration, and general transport were enriched in our screen, demonstrating pleiotropic effects of?ers1-Δ. These results give insight into yeast cystine regulation and the multiple, seemingly distal, pathways that involve proper cystine recycling.
机译：胱氨酸和半胱氨酸是诸如氧化还原信号传导和调节等途径的重要分子，因此在缺失酿酒酵母-胱氨酸转运蛋白Ers1p时鉴定细胞缺陷，可以进一步了解胱氨酸稳态。先前使用人类直系同源物进行的补充研究表明，酵母Ers1p是胱氨酸转运蛋白。人CTNS编码半胱氨酸蛋白，一种胱氨酸转运蛋白，嵌入在溶酶体膜中，并促进从溶酶体中输出胱氨酸。当“ CTNS”突变时，胱氨酸运输被破坏，导致胱氨酸蓄积，这是溶酶体贮积病胱氨酸病的诊断标志。在这里，我们提供Ers1p依赖的胱氨酸运输的生化证据。然而，当从Δers1-Δ酵母中缺失ΔERS1Δ基因时，未观察到细胞内胱氨酸的积累，这支持了修饰基因的存在，所述修饰基因提供了阻止或纠正胱氨酸积累的Δ1-ers酵母的机制。比较了βS的同基因ΔERS1+Δ和Δers1-Δ菌株的转录组。通过DNA芯片，随后进行定向qPCR鉴定啤酒酵母，鉴定出两种基因型之间差异表达的16个基因。编码在硫调节，细胞呼吸和一般运输中起作用的蛋白质的基因在我们的筛选中得到了丰富，证明了flers1-Δ的多效作用。这些结果使人们对酵母胱氨酸的调节以及涉及正确胱氨酸回收的多种看似远端的途径有了更深入的了解。

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