Department of Pathology, University of Michigan Medical School, Ann Arbor, MI USA.
Autophagy. 2012 May 1;8(5):719-30. doi: 10.4161/auto.19469.
Lysosomes are ubiquitous intracellular organelles that have an acidic internal pH, and play crucial roles in cellular clearance. Numerous functions depend on normal lysosomes, including the turnover of cellular constituents, cholesterol homeostasis, downregulation of surface receptors, inactivation of pathogenic organisms, repair of the plasma membrane and bone remodeling. Lysosomal storage disorders (LSDs) are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. As a consequence, many tissues and organ systems are affected, including brain, viscera, bone and cartilage. The progressive nature of phenotype development is one of the hallmarks of LSDs. In recent years biochemical and cell biology studies of LSDs have revealed an ample spectrum of abnormalities in a variety of cellular functions. These include defects in signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking. Lysosomes also play a fundamental role in the autophagic pathway by fusing with autophagosomes and digesting their content. Considering the highly integrated function of lysosomes and autophagosomes it was reasonable to expect that lysosomal storage in LSDs would have an impact upon autophagy. The goal of this review is to provide readers with an overview of recent findings that have been obtained through analysis of the autophagic pathway in several types of LSDs, supporting the idea that LSDs could be seen primarily as "autophagy disorders."
溶酶体是普遍存在于细胞内的细胞器，其内部 pH 值呈酸性，在细胞清除过程中发挥着至关重要的作用。许多功能依赖于正常的溶酶体，包括细胞成分的更新、胆固醇稳态、表面受体的下调、病原体的失活、质膜的修复和骨重塑。溶酶体贮积症（LSDs）的特征是由于溶酶体功能障碍，细胞内未消化的大分子物质逐渐积累。因此，许多组织和器官系统受到影响，包括大脑、内脏、骨骼和软骨。表型发展的进行性是 LSDs 的特征之一。近年来，对 LSDs 的生化和细胞生物学研究揭示了各种细胞功能中大量的异常。这些异常包括信号通路、钙稳态、脂质生物合成和降解以及细胞内运输的缺陷。溶酶体还通过与自噬体融合并消化其内容物，在自噬途径中发挥着基本作用。考虑到溶酶体和自噬体的高度整合功能，溶酶体贮积在 LSDs 中会对自噬产生影响是合理的。本文的目的是为读者提供一个概述，介绍通过分析几种 LSDs 中的自噬途径获得的最新发现，支持 LSDs 主要可以被视为“自噬障碍”的观点。
