mTORC1 regulates autophagosomal components recycling through SNX16 phosphorylation
Abstract
During autophagy, the contents enclosed within autophagosomes are degraded, while the outer membrane components are recycled from autolysosomes by the recycler complex through the recently discovered autophagosomal components recycling (ACR) process. This recycling is essential for maintaining autophagic activity. However, the molecular machinery and upstream regulatory mechanisms driving this recycling process remain poorly understood. Here, we identify SNX16 as a key component of the recycler complex, which localizes to autolysosomes and is required for ACR. SNX16 functions in ACR by regulating recycler complex formation, facilitating cargo recognition, and mediating the connection between STX17–SNX4–SNX5 and dynein–dynactin complexes. In addition, SNX16–cargo interactions are regulated by two ACR-related small GTPases, Rab32 and Rab38. Importantly, mTORC1 phosphorylates SNX16 to regulate ACR by inhibiting its interactions with STX17 and other recycler components, thus preventing recycler complex formation. Taken together, our findings identify SNX16 as a recycler component and establish a link between mTORC1 and ACR.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (10)
Huilin Que
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology
Fengping Liu
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology
Yang Chen
Wenmin Tian
Department of Biochemistry and Molecular Biology, Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Peking University
Shuaixin Gao
Human Nutrition Program and James Comprehensive Cancer Center, Ohio State University
Catherine C. L. Wong
Yan Li
Shixuan Wang
Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry
Xianbin Meng
Equipment R&D Center, Shenzhen Medical Academy of Research and Translation
Yueguang Rong
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology