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首页> 外文期刊>PLoS Genetics >Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis
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Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis

机译：计算驱动的定量实验发现线粒体生物发生所需的基因

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Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an increase of about 25% over previously known participants. Nearly half of these newly characterized proteins are conserved in mammals, including several orthologs known to be involved in human disease. Mutations in many of these genes demonstrate statistically significant mitochondrial transmission phenotypes more subtle than could be detected by traditional genetic screens or high-throughput techniques, and 47 have not been previously localized to mitochondria. We further characterized a subset of these genes using growth profiling and dual immunofluorescence, which identified genes specifically required for aerobic respiration and an uncharacterized cytoplasmic protein required for normal mitochondrial motility. Our results demonstrate that by leveraging computational analysis to direct quantitative experimental assays, we have characterized mutants with subtle mitochondrial defects whose phenotypes were undetected by high-throughput methods.
机译：线粒体对于许多细胞过程至关重要，包括呼吸，离子稳态和凋亡。使用计算预测与传统的定量实验相结合，我们已经鉴定出100种蛋白质，这些蛋白质的缺乏会改变酿酒酵母中的线粒体生物发生和遗传。此外，我们使用计算预测来执行针对性的双突变分析，以检测另外9个线粒体生物发生中具有合成缺陷的基因。这比以前已知的参与者增加了约25％。这些新近鉴定的蛋白质中近一半在哺乳动物中得以保存，包括几种已知与人类疾病有关的直系同源物。与传统的遗传筛选或高通量技术相比，许多这些基因中的突变显示出统计学上显着的线粒体传递表型更加微妙，并且47以前尚未定位于线粒体。我们使用生长谱和双重免疫荧光进一步表征了这些基因的一个子集，该基因鉴定出了有氧呼吸特别需要的基因和正常线粒体运动所需的未表征的细胞质蛋白。我们的结果表明，通过利用计算分析直接进行定量实验分析，我们已经表征了具有细微线粒体缺陷的突变体，这些突变体的表型无法通过高通量方法检测到。

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