Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Japan.
FEBS J. 2019 Jan;286(2):232-240. doi: 10.1111/febs.14589. Epub 2018 Jun 30.
Various types of intracellular and extracellular stresses disturb homeostasis in the endoplasmic reticulum (ER) and, thus, trigger the ER stress response. Unavoidable and/or prolonged ER stress causes cell toxicity and occasionally cell death. The malfunction or death of irreplaceable cells leads to conformational diseases, including diabetes mellitus, ischemic diseases, metabolic diseases, and neurodegenerative diseases. In the past several decades, many studies have revealed the molecular mechanisms of the ER quality control system. Cells resolve ER stress by promptly and accurately reducing the amount of malfolded proteins. Recent reports have revealed that cells possess several types of ER-related disposal systems, including mRNA decay, proteasomal degradation, and autophagy. The removal of dispensable RNAs, proteins, and organelle parts may enable the effective maintenance of a functional ER. Here, we provide a comprehensive understanding of the ER quality control system by focusing on ER-related garbage disposal systems.
各种类型的细胞内和细胞外应激会破坏内质网（ER）的内稳态，从而引发内质网应激反应。不可避免和/或长期的内质网应激会导致细胞毒性，偶尔还会导致细胞死亡。不可替代细胞的功能障碍或死亡会导致构象疾病，包括糖尿病、缺血性疾病、代谢疾病和神经退行性疾病。在过去的几十年中，许多研究已经揭示了内质网质量控制系统的分子机制。细胞通过及时准确地减少错误折叠蛋白的数量来解决内质网应激。最近的报告表明，细胞具有多种类型的与内质网相关的处理系统，包括 mRNA 衰减、蛋白酶体降解和自噬。去除可有可无的 RNA、蛋白质和细胞器部分可以有效地维持内质网的功能。在这里，我们通过关注与内质网相关的垃圾处理系统，对内质网质量控制系统有一个全面的了解。
