Dynamin Regulates Autophagy by Modulating Lysosomal Function

Xuefei Fang^{a, #},
Jia Zhou^{a, #},
Wei Liu^a,
Xiuying Duan^a,
Upasana Gala^b,
Hector Sandoval^{c, d},
Manish Jaiswal^{c, e},
Chao Tong^{a
, ,}

a.
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China
b.
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
c.
Howard Hughes Medical Institute, Houston, TX 77030, USA
d.
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA
e.
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX 77030, USA

More Information

Corresponding author: E-mail address: ctong@zju.edu.cn (Chao Tong)

These authors contributed equally to this work.

摘要

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Abstract: Autophagy is a central lysosomal degradation pathway required for maintaining cellular homeostasis and its dysfunction is associated with numerous human diseases. To identify players in autophagy, we tested ∼1200 chemically induced mutations on the X chromosome in Drosophila fat body clones and discovered that shibire (shi) plays an essential role in starvation-induced autophagy. shi encodes a dynamin protein required for fission of clathrin-coated vesicles from the plasma membrane during endocytosis. We showed that Shi is dispensable for autophagy initiation and autophagosome–lysosome fusion, but required for lysosomal/autolysosomal acidification. We also showed that other endocytic core machinery components like clathrin and AP2 play similar but not identical roles in regulating autophagy and lysosomal function as dynamin. Previous studies suggested that dynamin directly regulates autophagosome formation and autophagic lysosome reformation (ALR) through its excision activity. Here, we provide evidence that dynamin also regulates autophagy indirectly by regulating lysosomal function.
- Dynamin /
- Autophagy /
- Endocytosis
These authors contributed equally to this work.
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