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arXiv · 2510.22179

Beyond Autophagy: VPS39 Deficiency Triggers Migrasome-Driven Stress Adaptation Revealed by Super-Resolution Imaging

Xuelei Pang·Weiyun Sun·Ning Jing·Wenwen Gong·Cuifang Kuang·Xu Liu·Hanbing Li·Yu-Hui Zhang·Yubing Han
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Abstract

Autophagy and migrasome formation constitute critical cellular mechanisms for maintaining cellular homeostasis, however, their potential compensatory interplay remains poorly understood. In this study, we identify VPS39, a core component of the HOPS complex, as a molecular switch coordinating these processes. Genetic ablation of VPS39 not only impairs autophagic flux but also triggers cell migration through RhoA/Rac1 GTPases upregulation, consequently facilitating migrasome formation. Using super-resolution microscopy, we further demonstrate that migrasomes serve as an alternative disposal route for damaged mitochondria during VPS39-induced autophagy impairment, revealing a novel stress adaptation mechanism. Our work establishes a previously unrecognized autophagy-migrasome axis and provides direct visual evidence of organelle quality control via migrasomal extrusion. These findings position VPS39-regulated pathway switching as a potential therapeutic strategy for neurodegenerative diseases characterized by autophagy dysfunction.

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Xuelei Pang, Weiyun Sun, Ning Jing, Wenwen Gong, Cuifang Kuang, Xu Liu, Hanbing Li, Yu-Hui Zhang, Yubing Han. 2025-10-25. Beyond Autophagy: VPS39 Deficiency Triggers Migrasome-Driven Stress Adaptation Revealed by Super-Resolution Imaging. https://arxiv.org/abs/2510.22179

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