Dynamin Regulates Autophagy by Modulating Lysosomal Function

Xuefei Fang, Jia Zhou, Wei Liu, Xiuying Duan, Upasana Gala, Hector Sandoval, Manish Jaiswal, Chao Tong

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)77-86
Number of pages10
JournalJournal of Genetics and Genomics
Volume43
Issue number2
DOIs
StatePublished - Feb 20 2016

Keywords

  • Journal Article
  • Research Support, Non-U.S. Gov't

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