Szegezdi Eva, Logue Susan E, Gorman Adrienne M, Samali Afshin
Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland, University Road, Galway, Ireland.
EMBO Rep. 2006 Sep;7(9):880-5. doi: 10.1038/sj.embor.7400779.
The efficient functioning of the endoplasmic reticulum (ER) is essential for most cellular activities and survival. Conditions that interfere with ER function lead to the accumulation and aggregation of unfolded proteins. ER transmembrane receptors detect the onset of ER stress and initiate the unfolded protein response (UPR) to restore normal ER function. If the stress is prolonged, or the adaptive response fails, apoptotic cell death ensues. Many studies have focused on how this failure initiates apoptosis, as ER stress-induced apoptosis is implicated in the pathophysiology of several neurodegenerative and cardiovascular diseases. In this review, we examine the role of the molecules that are activated during the UPR in order to identify the molecular switch from the adaptive phase to apoptosis. We discuss how the activation of these molecules leads to the commitment of death and the mechanisms that are responsible for the final demise of the cell.
内质网（ER）的高效运作对大多数细胞活动和生存至关重要。干扰内质网功能的状况会导致未折叠蛋白的积累和聚集。内质网跨膜受体检测到内质网应激的发生，并启动未折叠蛋白反应（UPR）以恢复正常的内质网功能。如果应激持续存在，或者适应性反应失败，就会引发凋亡性细胞死亡。许多研究聚焦于这种失败如何引发凋亡，因为内质网应激诱导的凋亡与几种神经退行性疾病和心血管疾病的病理生理学有关。在本综述中，我们研究了在未折叠蛋白反应过程中被激活的分子的作用，以便确定从适应阶段到凋亡的分子开关。我们讨论这些分子的激活如何导致细胞走向死亡以及负责细胞最终死亡的机制。
