Dipartimento di Chimica e Biologia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (Salerno), Italy.
Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (Salerno), Italy.
Int J Mol Sci. 2020 Mar 11;21(6):1905. doi: 10.3390/ijms21061905.
The endoplasmic reticulum (ER) is a dynamic organelle essential for intracellular homeostasis maintenance, controlling synthesis, the folding of secreted and membrane-bound proteins, and transport of Ca. During cellular stress, ER dysfunction leads to the activation of unfolded protein response (UPR) due to accumulated misfolded proteins in the ER. This condition is referred as ER stress. Mitochondria and ER form a site of close contact (the mitochondria-associated membrane, MAM) which is a major platform exerting important physiological roles in the regulation of intracellular Ca homeostasis, lipid metabolism, mitochondrial fission, autophagosome formation, and apoptosis progression. Natural products have been receiving increasing attention for their ability to interfere with ER stress. Research works have focused on the capacity of these bioactive compounds to induce apoptosis by activating ER stress through the ER stress-mediated mitochondrial apoptotic pathway. In this review we discuss the role of natural products in the signaling communication between ER and mitochondria, focusing on the effects induced by ER stress including Ca permeability transition and UPR signaling (protein kinase R-like ER kinase/mitofusin 2).
内质网（ER）是一种动态细胞器，对于维持细胞内稳态至关重要，它控制着分泌蛋白和膜结合蛋白的合成、折叠和运输 Ca。在细胞应激时，由于 ER 中积累的错误折叠蛋白，ER 功能障碍会导致未折叠蛋白反应（UPR）的激活。这种情况被称为 ER 应激。线粒体和 ER 形成紧密接触的部位（线粒体相关膜，MAM），这是一个重要的平台，在调节细胞内 Ca 稳态、脂质代谢、线粒体裂变、自噬体形成和细胞凋亡进展方面发挥着重要的生理作用。天然产物因其干扰 ER 应激的能力而受到越来越多的关注。研究工作集中在这些生物活性化合物通过 ER 应激介导的线粒体凋亡途径激活 ER 应激诱导细胞凋亡的能力上。在这篇综述中，我们讨论了天然产物在 ER 和线粒体之间信号通讯中的作用，重点讨论了 ER 应激诱导的 Ca 通透性转换和 UPR 信号（蛋白激酶 R 样内质网激酶/线粒体融合蛋白 2）的作用。
