线粒体功能障碍是帕金森病（PD）的发病机制之一。线粒体ATP合成酶结构及功能稳定是线粒体发挥生理功能的保障。线粒体相关基因CHCHD2 182CT突变可导致常染色体显性遗传性PD。我们前期研究证实：CHCHD2可抵抗α-Syn的细胞毒性及MPP+诱导的线粒体功能障碍；沉默CHCHD2导致线粒体ATP合成酶活性降低，且CHCHD2与线粒体ATP合成酶亚基OSCP存在相互作用。但CHCHD2调控线粒体ATP合成酶在PD中的作用机制仍不清楚。本项目在前期工作基础上，采用免疫共沉淀、膜片钳技术、立体定位注射等方法，在分子、细胞、整体水平研究CHCHD2通过OSCP对线粒体ATP合成酶的调控作用机制，阐明182CT突变型的致病效应，分析CHCHD2靶向线粒体ATP合成酶对α-Syn细胞毒性的影响，以揭示CHCHD2在PD中的作用机制，对阐明CHCHD2线粒体作用机制及寻找PD新治疗靶点具有重要意义。

Mitochondrial dysfunction plays a pivotal role in Parkinson's disease (PD). The structure integrity and function stability of mitochondrial ATP synthase maintain the physiological functions of mitochondria. The 182CT missense mutation in CHCHD2, a mitochondrial related gene, is associated with autosomal dominant Parkinson's disease. Our previous studies found: Overexpression CHCHD2 can protect against toxicity of α-Syn and MPP+ induced mitochondrial dysfunction. CHCHD2-knockdown resulted in impairment of mitochondrial ATP synthase. CHCHD2 can interact with OSCP, a subunit of mitochondrial ATP synthase. However, the mechanisms of CHCHD2 in regulating the mitochondrial ATP synthase in PD still remain obscure. Based on our previous researches, we will investigate the interaction of CHCHD2 with OSCP to regulate mitochondrial ATP synthase at molecular, cellular and tissue levels with methods of Co-immunoprecipitation, Serotype injection and Patch clamp, etc. The pathogenic effect of CHCHD2 182CT mutant will also be discussed. Furthermore, to illustrate the role of CHCHD2 in PD, we will investigate the cross-talk of CHCHD2 with mitochondrial ATP synthase in inhibiting toxicity of α-Syn and find the relevant mechanisms. This study will further improve our understanding on the role of CHCHD2 in mitochondria and provide potential therapeutic target for PD.