title: Dynamin Regulates Autophagy by Modulating Lysosomal Function.
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.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Fang
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Duan
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Upasana
authors.initials: U
authors.lastname: Gala
authors.affiliation: Howard Hughes Medical Institute, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Hector
authors.initials: H
authors.lastname: Sandoval
authors.affiliation: Howard Hughes Medical Institute, Houston, TX 77030, USA; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Jaiswal
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China. Electronic address: ctong@zju.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Tong
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000235:genetics; D002478:Cells, Cultured; D002966:Clathrin / Q000502:physiology; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D034285:Dynamin II / Q000502:physiology; D034281:Dynamins / Q000235:genetics / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism*; D009154:Mutation; D051381:Rats
chemical_list: D033962:Adaptor Protein Complex 2; D002966:Clathrin; D029721:Drosophila Proteins; D034285:Dynamin II; D034281:Dynamins; C439628:shi protein, Drosophila
keywords: Autophagy; Drosophila; Dynamin; Endocytosis