REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-213, Porto, Portugal.
REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-213, Porto, Portugal.
Pharmacol Res. 2020 May;155:104702. doi: 10.1016/j.phrs.2020.104702. Epub 2020 Feb 14.
The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. Disturbed ER homeostasis triggers the activation of a conserved molecular machinery, termed the unfolded protein response (UPR), that comprises three major signaling branches, initiated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and the activating transcription factor 6 (ATF6). Given the impact of this intricate signaling network upon an extensive list of cellular processes, including protein turnover and autophagy, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the essentials on the current knowledge of the molecular biology of endoplasmic reticulum stress, while highlighting the available tools used in studies of this nature.
内质网（ER）由管状和囊泡构成，是真核细胞中最大的细胞器。内质网是大多数蛋白质合成和折叠的场所，对于维持细胞内环境的稳定至关重要。内质网稳态的破坏会触发一种保守的分子机制的激活，称为未折叠蛋白反应（UPR），它由三种主要的信号分支组成，由蛋白激酶 RNA 样内质网激酶（PERK）、肌醇需求酶 1（IRE1）和激活转录因子 6（ATF6）启动。鉴于这个复杂的信号网络对包括蛋白质周转和自噬在内的广泛细胞过程的影响，内质网应激参与了多种疾病的发生和发展，包括癌症和神经退行性疾病。因此，越来越多的出版物专注于描述和/或调节内质网应激，这导致了广泛使用的技术来研究与内质网相关的分子事件。这篇综述旨在总结内质网应激的分子生物学的最新知识要点，同时强调了用于此类研究的可用工具。
