Autonhagy Regulation Mechanism Of Endocytic Protein Shibire In Drosophila

Damaged proteins or organelles will be produced in the metabolic process of cell and these damaged proteins or organelles must be cleared in time. Otherwise, it will affect the normal metabolic activities of cells. Autophagy is one of the important pathways to remove them. Abnormal autophagy will cause varieties of human diseases such as neurodegenerative diseases, heart disease, liver disease, premature aging and so on. Therefore, exploring the mechanism of autophagy have an important role for human health.To identify players in autophagy, we tested-1,200EMS induced mutations on the X-chromosome in Drosophila and discovered that shibire (shi) plays an essential role in autophagy. We show that Shi is dispensable for autophagy initiation and autophagosome-lysosome fusion, but required for lysosomal/autolysosomal acidification. Lysosomal dysfunction in shi mutants is due to trafficking defects of lysosomal proteins, including vATPase subunits. These lysosomal defects are independent of the autophagy induce. We also show that other endocytic core machinery components like clathrin, API and AP2play 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 and ALR indirectly by regulating lysosomal protein trafficking and mTOR reactivation.