乙酰化在调控细胞自噬发生过程中的分子机制与功能的研究

细胞自噬是一种依赖于溶酶体（或是液泡）的物质降解途径。大量研究表明，自噬功能的异常与许多疾病如老年性痴呆症、癌症、免疫性系统疾病、病原体侵染等的发生发展有着非常密切的联系。申请人前期研究发现，乙酰化对在氮源饥饿和血清饥饿条件下诱导的自噬起着非常重要的调控作用。研究表明，当对细胞进行去乙酰化酶抑制剂处理时，自噬能够被诱导起来。去乙酰化酶抑制剂在临床上也已经作为抗癌药物使用。但到目前为止，我们对于细胞如何通过增强其乙酰化作用来自发诱导自噬发生的分子机制及其生理意义并不清楚。本课题拟在前期研究基础上，以酵母和哺乳细胞为研究材料，综合利用遗传学，细胞生物学等多种手段，致力于较为全面系统的阐述乙酰化作用自发诱导自噬发生的蛋白质机器、分子机制、信号通路、降解底物及其生理意义。该项目的研究将进一步完善乙酰化调控细胞自噬发生的分子调控网络，也能为预防和治疗由于自噬功能异常所引发的疾病提供新的靶点和策略。

Autophagy is a biological process which degrades material through lysosome or vacuole. A large number of studies have shown that the dysfunction of autophagy is closely related to the occurrence and development of Neurodegenerative diseases, cancer, immune system disease, pathogen infection etc. Our previous study found that acetylation plays an important role in the regulation of autophagy induced by nitrogen starvation and serum starvation. It was found that autophagy could be induced when cells were treated with histone deacetylase（HDAC） inhibitor, HDAC inhibitors have also been used as anti-cancer drugs in clinical practice. But so far, we do not know the molecular mechanism and the physiological significance of acetylation how to induce autophagy. This project is based on yeast and mammalian cells as research materials, the comprehensive utilization of genetics, cell biology and other means, to systematically illustrate protein machinery, molecular mechanism, signaling pathway, substrate degradation and physiological significance of acetylation-induced autophagy spontaneously. This project will further enrich the molecular regulation network of acetylation regulation of autophagy, and provide new targets and strategies for the prevention and treatment of diseases caused by the dysfunction of autophagy.