We have recently reported on an experimental model of mitochondrial mistranslation conferred by amino acid exchange V338Y in the mitochondrial ribosomal protein MrpS5. Here we used a combination of RNA-Seq and metabolic profiling of homozygous transgenic MrpS5V338Y/V338Y mice to analyze the changes associated with the V338Y mutation in post-mitotic skeletal muscle. Metabolic profiling demonstrated age-dependent metabolic changes in the mutant V338Y animals, which included enhanced levels of age-associated metabolites and which were accompanied by increased glycolysis, lipid desaturation and eicosanoid biosynthesis, and alterations of the pentose phosphate pathway. In addition, transcriptome signatures of aged V338Y mutant muscle pointed to elevated inflammation, likely reflecting the increased levels of bioactive lipids. Our findings indicate that mistranslation-mediated chronic impairment of mitochondrial function affects specific bioenergetic processes in muscle in an age-dependent manner.

中文翻译：

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骨骼肌中的线粒体误读会加速代谢衰老并导致脂质积累和炎症增加


我们最近报道了线粒体核糖体蛋白 MrpS5 中氨基酸交换 V338Y 赋予的线粒体误译实验模型。在这里，我们结合使用 RNA 测序和纯合转基因 MrpS5V338Y/V338Y 小鼠的代谢分析来分析与有丝分裂后骨骼肌中 V338Y 突变相关的变化。代谢分析表明，突变型 V338Y 动物存在年龄依赖性代谢变化，其中包括与年龄相关的代谢物水平升高，并伴有糖酵解、脂质去饱和和类二十烷酸生物合成增加，以及磷酸戊糖途径的改变。此外，衰老的 V338Y 突变肌肉的转录组特征表明炎症加剧，可能反映了生物活性脂质水平的增加。我们的研究结果表明，错误翻译介导的线粒体功能慢性损伤以年龄依赖性方式影响肌肉中的特定生物能过程。