Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Autophagy. 2022 Oct;18(10):2498-2499. doi: 10.1080/15548627.2022.2095788. Epub 2022 Jul 14.
Both macroautophagy/autophagy and extracellular vesicle (EV) secretion pathways converge upon the endolysosome system. Although lysosome impairment leads to defects in autophagic degradation, the impact of such dysfunction on EV secretion remains poorly understood. Recently, we uncovered a novel secretory autophagy pathway that employs EVs and nanoparticles (EVPs) for the secretion of autophagy cargo receptors outside the cell when either autophagosome maturation or lysosomal function is blocked. We term this process secretory autophagy during lysosome inhibition (SALI). SALI functionally requires multiple steps in classical autophagosome formation and the small GTPase RAB27A. Because the intracellular accumulation of autophagy cargo receptors perturbs cell signaling and quality control pathways, we propose that SALI functions as a failsafe mechanism to preserve protein and cellular homeostasis when autophagic or lysosomal degradation is impaired.
自噬/吞噬作用和细胞外囊泡 (EV) 分泌途径都集中在内体溶酶体系统。虽然溶酶体功能障碍会导致自噬降解缺陷，但这种功能障碍对 EV 分泌的影响仍知之甚少。最近，我们发现了一种新的分泌自噬途径，当自噬体成熟或溶酶体功能被阻断时，该途径利用 EV 和纳米颗粒 (EVPs) 将自噬货物受体分泌到细胞外。我们将这个过程称为溶酶体抑制时的分泌自噬 (SALI)。SALI 在功能上需要经典自噬体形成的多个步骤和小 GTPase RAB27A。由于自噬货物受体在细胞内的积累会扰乱细胞信号转导和质量控制途径，因此我们提出，当自噬或溶酶体降解受损时，SALI 作为一种故障安全机制发挥作用，以维持蛋白质和细胞的动态平衡。
