Exosomes are small vesicles that are secreted from cells to dispose of undegraded materials and mediate intercellular communication. A major source of exosomes is intraluminal vesicles within multivesicular endosomes that undergo exocytic fusion with the plasma membrane. An alternative fate of multivesicular endosomes is fusion with lysosomes, resulting in degradation of the intraluminal vesicles. The factors that determine whether multivesicular endosomes fuse with the plasma membrane or with lysosomes are unknown. In this study, we show that impairment of endolysosomal fusion by disruption of a pathway involving the BLOC-one-related complex (BORC), the small GTPase ARL8, and the tethering factor HOPS increases exosome secretion by preventing the delivery of intraluminal vesicles to lysosomes. These findings demonstrate that endolysosomal fusion is a critical determinant of the amount of exosome secretion and suggest that suppression of the BORC–ARL8–HOPS pathway could be used to boost exosome yields in biotechnology applications.

中文翻译：

---

抑制内溶酶体融合增加外泌体分泌

外泌体是细胞分泌的小囊泡，用于处理未降解的物质并介导细胞间通讯。外泌体的主要来源是多囊泡内体中的腔内囊泡，其与质膜进行胞吐融合。多囊泡内体的另一种命运是与溶酶体融合，导致腔内囊泡降解。决定多囊泡内体是否与质膜或溶酶体融合的因素尚不清楚。在这项研究中，我们发现，通过破坏涉及 BLOC-one 相关复合物 (BORC)、小 GTPase ARL8 和束缚因子 HOPS 的通路来损害内溶酶体融合，通过阻止腔内囊泡递送至溶酶体来增加外泌体分泌。这些发现表明，内溶酶体融合是外泌体分泌量的关键决定因素，并表明抑制 BORC-ARL8-HOPS 途径可用于提高生物技术应用中的外泌体产量。