Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
J Cell Biol. 2010 May 31;189(5):783-94. doi: 10.1083/jcb.201003138.
The extensive membrane network of the endoplasmic reticulum (ER) is physically juxtaposed to and functionally entwined with essentially all other cellular compartments. Therefore, the ER must sense diverse and constantly changing physiological inputs so it can adjust its numerous functions to maintain cellular homeostasis. A growing body of new work suggests that the unfolded protein response (UPR), traditionally charged with signaling protein misfolding stress from the ER, has been co-opted for the maintenance of basal cellular homeostasis. Thus, the UPR can be activated, and its output modulated, by signals far outside the realm of protein misfolding. These findings are revealing that the UPR causally contributes to disease not just by its role in protein folding but also through its broad influence on cellular physiology.
内质网（ER）的广泛膜网络在物理上与几乎所有其他细胞区室并列，并在功能上交织在一起。因此，内质网必须感知各种不断变化的生理输入，以便能够调整其众多功能以维持细胞内稳态。越来越多的新工作表明， unfolded protein response (UPR) 传统上负责从 ER 发出蛋白质错误折叠应激信号，已被用于维持基础细胞内稳态。因此，UPR 可以被蛋白质错误折叠之外的信号激活，并调节其输出。这些发现表明，UPR 通过其在蛋白质折叠中的作用导致疾病，也通过其对细胞生理学的广泛影响导致疾病。
