内质网应激调控细胞自噬和凋亡

Endoplasmic Reticulum Stress Regulates Cell Autophagy and Apoptosis

内质网是真核细胞中蛋白质合成、折叠与分泌的重要膜性细胞器。当内源或外源性的刺激导致内质网的蛋白质折叠功能发生紊乱时,内质网腔内累积大量未折叠或错误折叠的蛋白质,并引起一系列后续反应称为内质网应激。此时,细胞启动未折叠蛋白反应,以清除未折叠蛋白并恢复内质网稳态。当内质网应激持续时,未折叠蛋白反应并不足以清除越积越多的未折叠蛋白,也无法去除受损伤的细胞器,细胞自噬被激活。当内质网应激过强或持续时间过长时,过度激活的自噬最终引起细胞死亡。该文就近年来内质网应激调控细胞自噬和细胞凋亡机制的研究进行综述,以期为相关领域的研究者提供新的思路。

Endoplasmic reticulum （ER） is an important membranous organelle for protein synthesis, folding and secretion in eukaryotic cells. Endogenous or exogenous stimuli, however, can lead to an imbalance between the ER protein folding capacity and protein load, giving rise to an accumulation of unfolded or misfolded proteins in the ER lumen, a condition dubbed as ＇ER stress＇. In an attempt to meet the increased folding demand, cells utilize a conserved signaling pathway, the unfolded protein response （UPR）, which is initially charged to restore the homeostasis of endoplasmic reticulum. If this mechanism fails, persistent ER stress will eventually cause this cytoprotective UPR to switch into a autophagy pathway or even a cell death pathway. In this paper, we reviewed recent studies on mechanisms of ER stress-induced autophagy and apoptosis, which may provide relevant information for the researchers.