线粒体相关内质网膜（MAMs）连结了内质网与线粒体，是调节细胞代谢、增殖、分化和凋亡的重要细胞功能区域之一。其功能的异常与神经退行性疾病的发生和发展息息相关。本项目致力于使用创新的ACUMEN-APEX2内源动态蛋白互作检测技术及MUSE生物信息学算法，以特异性地捕获瞬时、微弱的蛋白动态结合，在SH-SY5Y神经细胞系中建立一个优质、定量、多维度的动态内源线粒体-内质网蛋白质互作网络，揭示线粒体相关内质网膜核心蛋白的结合、转运及相互调节的关系，筛选和发现介导线粒体与内质网细胞器互作的关键蛋白并阐明其作用机制。通过研究生理及病理状态下线粒体相关内质网膜的蛋白质互作网络重编程，阐明其蛋白质复合物形成及功能调节的分子机制，理解线粒体与内质网协同调节物质与能量代谢的原理，从而为诊断与治疗包括多种神经退行性疾病在内的复杂疾病提供新的理论基础、生物标记和药物靶点。

Mitochondria-associated endoplasmic reticulum membrane (MAMs) connects endoplasmic reticulum and mitochondria, and regulates cell metabolism, proliferation, differentiation and apoptosis. Its dysfunction has been linked to the initiation and maintenance of multiple neurodegenerative diseases. The goal of this study is to adopt cutting-edge mass spectrometry technologies such as ACUMEN-APEX2 method in human system to detect weak and transient protein-protein interactions, and MUSE algorithm to quantitatively analyze the data, to establish a high-quality, quantitative and multi-dimensional dynamic endogenous protein-protein interaction network of MAMs in SH-SY5Y cells. It will highlight the dynamic signaling events under physiological and pathological conditions, reveal the composition, transportation and regulation of these protein complexes, elucidate the dynamic signaling events under physiological and pathological conditions, reveal connections between core pathway components and their regulators, and identify many novel biomarkers and drug targets for the diagnosis and treatment of related neurodegenerative diseases, and shed light on future disease-related signaling network research.