内质网应激诱导自噬的分子机制

在真核细胞中,内质网对蛋白质的折叠和运输至关重要,多种病理因素对内质网稳态的扰乱,可导致内质网腔中未折叠或错误折叠蛋白蓄积,即内质网应激(ERS)。细胞为此通过激活一种叫做未折叠蛋白反应(UPR)的防御反应来恢复内质网稳态。自噬是一种被描述为"自我吞食"的细胞代谢过程,其通过批量清除和降解未折叠蛋白以及破损细胞器在ERS时作为一种重要的保护机制。近年的研究显示这两个系统动态互联,且ERS可以通过多种方式诱导自噬的发生。在本文中,我们将总结目前关于ERS尤其是UPR诱导自噬的分子机制的相关知识,以进一步指导关于ERS与自噬关系的的研究。

The Molecular Mechanism of Autophagy Induced by Endoplasmic Reticulum Stress

ABSTRACT: In eukaryotic cells, the endoplasmic reticulum(ER) is essential for the folding and translocation of proteins. The dis- turbance of the endoplasmic reticulum homeostasis, caused by multiple pathological factors will lead to the accumulation of unfolded or misfolded proteins in the ER lumen, known as endoplasmic reticulum stress(ERS). Cells react to ERS by activating an defensive process known as the Unfolded Protein Response (UPR) to restore the endoplasmic reticulum homeostasis. Autophagy is a cellular catabolic pro- cess which can be described as a "self-eating", it emerged as an essential protective mechanism upon ER stress through the bulk removal and degradation of unfolded proteins and damaged organelles. Recent studies show that these 2 systems are interconnected, and the ER stress can induce autophagy in a variety of ways. In this review, we will summarize the current knowledge about the molecular mecha- nism of autophagy by Endoplasmic Reticulum Stress especially the UPR, to guide further study on ER stress and autophagy.