Braulke Thomas, Carette Jan E, Palm Wilhelm
Department of Osteology and Biomechanics, Cell Biology of Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Trends Cell Biol. 2024 Mar;34(3):198-210. doi: 10.1016/j.tcb.2023.06.005. Epub 2023 Jul 18.
Lysosomes degrade and recycle macromolecules that are delivered through the biosynthetic, endocytic, and autophagic routes. Hydrolysis of the different classes of macromolecules is catalyzed by about 70 soluble enzymes that are transported from the Golgi apparatus to lysosomes in a mannose 6-phosphate (M6P)-dependent process. The molecular machinery that generates M6P tags for receptor-mediated targeting of lysosomal enzymes was thought to be understood in detail. However, recent studies on the M6P pathway have identified a previously uncharacterized core component, yielded structural insights in known components, and uncovered functions in various human diseases. Here we review molecular mechanisms of lysosomal enzyme trafficking and discuss its relevance for rare lysosomal disorders, cancer, and viral infection.
溶酶体降解并循环利用通过生物合成、内吞和自噬途径传递的大分子。不同种类大分子的水解由大约70种可溶性酶催化，这些酶在一个依赖于甘露糖6-磷酸（M6P）的过程中从高尔基体转运到溶酶体。人们曾认为，为受体介导的溶酶体酶靶向生成M6P标签的分子机制已被详细了解。然而，最近对M6P途径的研究发现了一个以前未被表征的核心成分，对已知成分有了结构上的认识，并揭示了其在各种人类疾病中的作用。在这里，我们综述溶酶体酶运输的分子机制，并讨论其与罕见溶酶体疾病、癌症和病毒感染的相关性。
