Atg11蛋白磷酸化和乙酰化修饰协同调控选择性自噬发生的分子机制研究

选择性自噬通过特定的受体与Atg8/LC3结合将相应的底物运输到溶酶体中进行降解。研究表明，选择性自噬在维持细胞稳态过程中起重要作用，其功能的异常与人类许多重大疾病如神经退行性疾病、外源病原体感染及癌症等的发生发展密切相关。Atg11，一个选择性自噬发生的标记蛋白，以衔接蛋白的形式分别与选择性自噬受体、Atg1和Atg8结合参与选择性自噬的发生。我们的前期工作发现，Atg11蛋白存在磷酸化和乙酰化两种修饰。Atg1参与了Atg11的磷酸化修饰，乙酰化酶Esa1参与了Atg11的乙酰化修饰，并且这两种修饰存在协同效应。本项目将在此基础上，阐明Atg11蛋白磷酸化和乙酰化修饰协同参与选择性自噬发生的分子机制。

Selective autophagy transfers the corresponding substrates to lysosomes for degradation by directly binding of Atg8/LC3 and specific receptors. Previous studies showed that selective autophagy plays an important role in maintaining cell homeostasis, and its abnormal function is closely related to the occurrence and development of many major human diseases, such as neurodegenerative diseases, exogenous pathogen infection and cancer. Atg11, a marker protein of selective autophagy, participates in selective autophagy by binding to selective autophagy receptor, Atg1 and Atg8 as adaptor protein. Our previous work found that Atg11 protein was modified by phosphorylation and acetylation. Atg1 phosphorylates Atg11, while the histone acetyltransferase Esa1 is involved in the acetylation of Atg11, and there is a synergistic effect between the two modifications. On this basis, our project will elucidate the molecular mechanism of Atg11 protein phosphorylation and acetylation synergistically regulating selective autophagy.