补体关键成分C3在肝细胞内介导自噬和调节脂代谢平衡的分子机制

补体关键成分C3在所有已知的补体激活途径中扮演重要角色，其主要来源于肝脏。补体C3主要在细胞表面发挥各种免疫应答功能，但其在肝细胞内部的生物学功能却从未被重视和探索。我们的前期工作发现，C3基因敲除小鼠相较于野生型小鼠肝脏内部呈现出加速的脂质累积，提示其在肝内的脂质代谢和平衡中扮演重要角色。本课题中，我们拟对C3缺失后，导致肝细胞自噬受损，并影响内质网和线粒体功能的分子机制做进一步的探索，寻找在肝细胞内和C3相互作用的分子，解析肝细胞内自噬和内质网功能之间的相互作用对肝内脂代谢平衡的调节机制。我们的工作将丰富人们对补体关键成分C3非免疫学功能的认识，促进人们对肝细胞内脂质代谢平衡分子机制的了解。

Complement component C3, mainly synthesized by hepatocytes, is the converge of three main pathways of complement activation. Apart from traditional activities of the complement system, including pathogen membrane attacking, chemotaxis, and opsonization in the extracellular milieu, it has become increasingly apparent that the complement component C3 has biological functions such as immunomodulation and pathogen recognition intracellularly. Our previous work has revealed that C3-deficient mice exhibited higher hepatic triglyceride levels compared to C57BL/6J wild type mice under normal diet. In addition, deficiency of C3 resulted in impaired autophagic flux and reduced VLDL secretion in the liver. In this project, we aim to disclose a novel mechanism by which intracellular C3 regulates hepatic lipid metabolism by mediating autophagy, and how C3 deficiency affects functions of endoplasmic reticulum and mitochondria intracellularly. Our study will provide a new insight into how intrahepatic lipid metabolism is regulated and endows a new physiological function for the complement component.