哺乳动物心脏为高能耗组织，其95%的ATP是在线粒体氧化呼吸链上产生。哺乳动物线粒体由1500余种蛋白质构成，大部分为核基因编码蛋白质，而由线粒体基因编码并由线粒体的核糖体完成翻译的蛋白质有13种，均定位在电子呼吸链上。本课题前期实验结果显示在小鼠病理肥厚模型的心肌组织和体外培养诱导的乳鼠心肌肥大模型中，线粒体核糖体蛋白S5(MRPS5)表达均明显下调；并且心肌特异敲除MRPS5小鼠出现线粒体稳态失衡与心功能障碍，提示MRPS5对维持线粒体与心脏功能的重要性。因此拟通过转录组学与代谢组学联合分析，探索MRPS5缺失引发的级联信号通路与分子机制; 并通过腺相关病毒(AAV9)对多组学联合分析得到的分子靶点进行成体功能性筛选，旨在发现靶向线粒体稳态失衡与心功能障碍的潜在治疗靶点。研究结果将为线粒体基因组缺陷相关疾病的研究提供新的动物模型，并为线粒体心血管疾病的研究提供理论基础与新的治疗策略。

The mammalian heart is an organ of highly demanding of energy, and the majority of ATP consumed by the heart (about 95%) is derived from oxidative phosphorylation in the mitochondria. Mammalian mitochondria are composed of more than 1500 proteins, and most of them are encoded by nuclear genomes, while mitochondrial genome only encodes 13 proteins, that are translated by mitochondrial ribosome and locate in the electronic respiratory chain. The preliminary results of this project showed that expression of mitochondrial ribosomal protein S5 (MRPS5) was significantly down-regulated both in the hypertrophic heart in transverse aorta constricted mice (in vivo) and in the hypertrophic cardiomyocytes induced by phenylephrine, isoproterenol, fetal bovine serum (in vitro). In addition, cardiac specific knockout of MRPS5 resulted in cardiac and mitochondrial dysfunction in mice， suggested that MRPS5 plays an important role in maintaining heart function and mitochondrial homeostasis. Therefore, a combined analysis of transcriptomics and metabolomics is proposed to explore the signaling pathway and underneath mechanism. By exploiting associated adenovirus 9 (AAV9) system, functional screening of potential targets obtained by the bi-omics combined analysis are aiming to identify true therapeutic targets for mitochondrial and heart dysfunction caused by MRPS5 deletion. The results will provide a wonderful animal model for studying of mitochondrial diseases and provide a theoretical basis and therapeutic strategy for mitochondrial cardiomyopathy.