Departament de Biomedicina, Unitat de Biologia Cellular, Facultat de Medicina i Ciències de la Salut, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
Bioessays. 2022 Oct;44(10):e2200111. doi: 10.1002/bies.202200111. Epub 2022 Aug 7.
NPC1 plays a central role in cholesterol egress from endolysosomes, a critical step for maintaining intracellular cholesterol homeostasis. Despite recent advances in the field, the full repertoire of molecules and pathways involved in this process remains unknown. Emerging evidence suggests the existence of NPC1-independent, alternative routes. These may involve vesicular and non-vesicular mechanisms, as well as release of extracellular vesicles. Understanding the underlying molecular mechanisms that bypass NPC1 function could have important implications for the development of therapies for lysosomal storage disorders. Here we discuss how cholesterol may be exported from lysosomes in which NPC1 function is impaired.
NPC1 在胆固醇从内溶酶体流出中发挥核心作用，这是维持细胞内胆固醇稳态的关键步骤。尽管该领域最近取得了进展，但涉及该过程的分子和途径的完整目录仍不清楚。新出现的证据表明存在 NPC1 独立的替代途径。这些途径可能涉及囊泡和非囊泡机制，以及细胞外囊泡的释放。了解绕过 NPC1 功能的潜在分子机制对于开发溶酶体贮积症的治疗方法可能具有重要意义。在这里，我们讨论了 NPC1 功能受损的溶酶体中胆固醇可能被输出的方式。
