Metcalf Melissa G, Higuchi-Sanabria Ryo, Garcia Gilberto, Tsui C Kimberly, Dillin Andrew
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, The Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
Sci Adv. 2020 Jul 15;6(29):eabb9614. doi: 10.1126/sciadv.abb9614. eCollection 2020 Jul.
The endoplasmic reticulum (ER) is commonly referred to as the factory of the cell, as it is responsible for a large amount of protein and lipid synthesis. As a membrane-bound organelle, the ER has a distinct environment that is ideal for its functions in synthesizing these primary cellular components. Many different quality control machineries exist to maintain ER stability under the stresses associated with synthesizing, folding, and modifying complex proteins and lipids. The best understood of these mechanisms is the unfolded protein response of the ER (UPR), in which transmembrane proteins serve as sensors, which trigger a coordinated transcriptional response of genes dedicated for mitigating the stress. As the name suggests, the UPR is most well described as a functional response to protein misfolding stress. Here, we focus on recent findings and emerging themes in additional roles of the UPR outside of protein homeostasis, including lipid homeostasis, autophagy, apoptosis, and immunity.
内质网（ER）通常被称为细胞的工厂，因为它负责大量蛋白质和脂质的合成。作为一种膜结合细胞器，内质网具有独特的环境，非常适合其在合成这些主要细胞成分方面的功能。存在许多不同的质量控制机制，以在与合成、折叠和修饰复杂蛋白质和脂质相关的压力下维持内质网的稳定性。其中最被理解的机制是内质网的未折叠蛋白反应（UPR），其中跨膜蛋白作为传感器，触发专门用于减轻压力的基因的协调转录反应。顾名思义，UPR最被描述为对蛋白质错误折叠压力的功能反应。在这里，我们关注UPR在蛋白质稳态之外的其他作用的最新发现和新兴主题，包括脂质稳态、自噬、细胞凋亡和免疫。
