Beyond Autophagy: VPS39 Deficiency Triggers Migrasome-Driven Stress Adaptation Revealed by Super-Resolution Imaging
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arXiv
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| Autori principali: | , , , , , , , , |
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| Natura: | Preprint |
| Pubblicazione: |
2025
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| _version_ | 1866917042238521344 |
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| author | Pang, Xuelei Sun, Weiyun Jing, Ning Gong, Wenwen Kuang, Cuifang Liu, Xu Li, Hanbing Zhang, Yu-Hui Han, Yubing |
| author_facet | Pang, Xuelei Sun, Weiyun Jing, Ning Gong, Wenwen Kuang, Cuifang Liu, Xu Li, Hanbing Zhang, Yu-Hui Han, Yubing |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2510_22179 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Beyond Autophagy: VPS39 Deficiency Triggers Migrasome-Driven Stress Adaptation Revealed by Super-Resolution Imaging Pang, Xuelei Sun, Weiyun Jing, Ning Gong, Wenwen Kuang, Cuifang Liu, Xu Li, Hanbing Zhang, Yu-Hui Han, Yubing Cell Behavior Biomolecules Subcellular Processes 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. |
| title | Beyond Autophagy: VPS39 Deficiency Triggers Migrasome-Driven Stress Adaptation Revealed by Super-Resolution Imaging |
| topic | Cell Behavior Biomolecules Subcellular Processes |
| url | https://arxiv.org/abs/2510.22179 |