Atg5 Regulates Late Endosome And Lysosome Biogenesis

Autophagy is an evolutionarily conserved lysosome-based degradation process. When cells are stimulated like starvation or ROS, autophagy happens. During autophagy, lysosomes fuse with autophagasomes to form the autolysososmes. In autolysosomes, the sequestered substrates are degraded into small molecules and transported out of autolysosomes for recyling. Atg5 plays a very important role in autophagosome formation especially in recruitment of Atg8（LC3）. Here we show that Atg5 is required for biogenesis of late endosomes and lysosomes in an autop hagy-independent manner. In Atg5^-/- Cells, but not in other essential autophagy genes defecting cells（Atg7, Atg12, Atg9 stably knowdown cells）, recycling and retrieval of late endosomal components from hybrid organelles are impaired, causing persistent hybrid organelles and defective formation of late endosomes and lysosomes. Retrieval of late endosomal components from hybrid organelles relies on pH-dependent manner regulated by V-ATPase recruitment. Our data show recruitment of V-ATPase to hybrid organelles is defected which results in increased pH environment in hybrid organelles. This causes defective retrieval of late endosomal components from hybrid organelles. Lowering the intracellular pH restores late endosome/lysosome biogenesis in Atg5^-/- Cells. Our data demonstrate an unexpected role of Atg5 and shed new light on late endosome and lysosome biogenesis.