Journal of Neuroimmune Pharmacology ( IF 5.2 ) Pub Date : 2021-03-22 , DOI: 10.1007/s11481-021-09990-7 Koffi L Lakpa 1 , Nabab Khan 1 , Zahra Afghah 1 , Xuesong Chen 1 , Jonathan D Geiger 1
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Extensive work has characterized endoplasmic reticulum (ER) and mitochondrial stress responses. In contrast, very little has been published about stress responses in lysosomes; subcellular acidic organelles that are physiologically important and are of pathological relevance. The greater lysosomal system is dynamic and is comprised of endosomes, lysosomes, multivesicular bodies, autophagosomes, and autophagolysosomes. They are important regulators of cellular physiology, they represent about 5% of the total cellular volume, they are heterogeneous in their sizes and distribution patterns, they are electron dense, and their subcellular positioning within cells varies in response to stimuli, insults and pH. These organelles are also integral to the pathogenesis of lysosomal storage diseases and it is increasingly recognized that lysosomes play important roles in the pathogenesis of such diverse conditions as neurodegenerative disorders and cancer. The purpose of this review is to focus attention on lysosomal stress responses (LSR), compare LSR with better characterized stress responses in ER and mitochondria, and form a framework for future characterizations of LSR. We synthesized data into the concept of LSR and present it here such that the definition of LSR can be modified as new knowledge is added and specific therapeutics are developed.
Graphical Abstract
中文翻译：
溶酶体应激反应 (LSR)：生理重要性和病理相关性
大量的工作已经描述了内质网 (ER) 和线粒体应激反应的特征。相比之下，关于溶酶体应激反应的报道却很少。亚细胞酸性细胞器，具有重要的生理学意义和病理学相关性。大溶酶体系统是动态的，由内体、溶酶体、多泡体、自噬体和自噬溶酶体组成。它们是细胞生理学的重要调节因子，约占细胞总体积的 5%，它们的大小和分布模式不同，它们具有电子密集性，并且它们在细胞内的亚细胞定位会因刺激、损伤和 pH 值而变化。这些细胞器也是溶酶体贮积病发病机制中不可或缺的一部分，人们越来越认识到溶酶体在神经退行性疾病和癌症等多种疾病的发病机制中发挥着重要作用。本综述的目的是关注溶酶体应激反应 (LSR)，将 LSR 与 ER 和线粒体中更好表征的应激反应进行比较，并为 LSR 的未来表征形成框架。我们将数据综合到 LSR 的概念中并将其呈现在此处，以便随着新知识的添加和特定疗法的开发，可以修改 LSR 的定义。
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