内质网与线粒体及高尔基体之间互作已有很多报道，但其调控的分子机制仍不清楚。细胞应激及病理过程中内质网与相关细胞器互作的功能及分子机制更有待研究。本项目在前期结果的基础上，分析定位于内质网的USP19和MARCH6在内质网和线粒体的相互作用过程中对于线粒体分裂相关蛋白的修饰以及功能的影响，以阐明内质网及其相关蛋白在线粒体分裂过程中的功能。同时，将利用不同诱导因素引起多种细胞应激反应，分析其在内质网与线粒体及高尔基体互作中的新功能。我们前期结果显示，在低氧处理或病原微生物侵染时，USP19和MARCH6分别影响线粒体的动态平衡和STING的激活。本项目将研究这些蛋白在内质网与相关细胞器互作中的功能和分子机理，并进一步寻找其它参与互作的未知蛋白，以完善细胞器互作在细胞应激中的调控机制。本项目的实施将揭示内质网与相关细胞器的互作网络、调控机制和生理功能，为相关疾病的防治提供理论依据。

The interactions of endoplasmic reticulum (ER) with mitochondrion or Golgi apparatus are increasingly recognized but the molecular mechanism regulating these interactions is only beginning to be unraveled. Moreover, the function and molecular mechanism of ER and associated organelle interactions under different physiological and pathological conditions remains largely unknown. In this project, we will analyses the function of USP19 and MARCH6, two ubiquitin-associated proteins localized at ER, in mitochondrial fission events, attempting to reveal the relationship between ER and mitochondrial dynamics. We will also investigate the interactions of ER with mitochondrion or Golgi apparatus in multiple cellular stress, including hypoxia or pathogens invading. Our preliminary data showed that USP19 regulated mitochondrial dynamics under hypoxia, and that MARCH6 activated STING. Besides, we will identify new proteins involved, and investigate the role of them in ER and other organelle interactions. This project will contribute to better understanding dynamic organelle networks and physiological functions of these contacts, and provide a theoretical basis for prevention and treatment of related diseases.