酵母必需基因蛋白敲低文库的建立及半胱氨酰-tRNA合成酶Crs1调控细胞自噬发生的分子机制及生理功能研究

细胞自噬是一类在进化过程中高度保守的依赖于溶酶体/液泡的物质降解途径。研究表明，自噬在维持细胞稳态和有机体正常生长发育过程中起重要作用。自噬功能的异常与外源病原体感染、神经退行性疾病、心血管疾病及癌症的发生发展密切相关。尽管近年来我们对自噬发生的分子机制和生理功能研究取得了很大进步，但对于基础自噬发生的分子机制的认识还有待提高。我们通过构建酵母必需基因蛋白降解文库，发现半胱氨酰-tRNA合成酶Crs1的降解能够自发诱导自噬，参与细胞基础自噬的调控。通过检测其mTORC1和Snf1/AMPK的活性，发现Crs1蛋白降解诱导的自噬既不是因为mTORC1活性的降低，也不是因为Snf1/AMPK的激活，表明其存在着另外一条诱导自噬发生的信号通路。基于此，我们将在前期的工作基础上，深入解析并阐述半胱氨酰-tRNA合成酶Crs1参与细胞基础自噬发生的分子调控机制及生理功能。

Autophagy is a highly conserved lysosome/vacuole-dependent material degradation pathway. Autophagy plays an important role in maintaining cell homeostasis and normal growth and development of organism. The dysfunction of autophagy is closely related to the occurrence and development of exogenous pathogen infection, neurodegenerative diseases, cardiovascular diseases and cancer. Although we have made great progress in the study of molecular mechanism and physiological function of autophagy in recent years, the molecular mechanism of basal autophagy is not fully understood. Through the construction of yeast essential proteins degradation library, we found that the degradation of Crs1 protein, a cysteinyl-tRNA synthetase, can spontaneously induce autophagy and participate in the regulation of basal autophagy. By detecting the activity of mTORC1 and Snf1/AMPK, we found that autophagy induced by Crs1 protein degradation was not due to the decrease of mTORC1 activity or the activation of Snf1 / AMPK, which indicated that there was another signal pathway inducing autophagy. Based on these results, we will further analyze and elaborate the molecular regulatory mechanism and physiological significance of Crs1 participation in basal autophagy.