Basal Autophagy Is Required for the Efficient Catabolism of Sialyloligosaccharides

Macroautophagy is an essential, homeostatic process involving degradation of a cell's own components; it plays a role in catabolizing cellular components, such as protein or lipids, and damaged or excess organelles. Here, we show that in Atg5 −/− cells, sialyloligosaccharides specifically accumulated in the cytosol. Accumulation of these glycans was observed under non-starved conditions, suggesting that non-induced, basal autophagy is essential for their catabolism. Interestingly, once accumulated in the cytosol, sialylglycans cannot be efficiently catabolized by resumption of the autophagic process, suggesting that functional autophagy is important for preventing sialyloligosaccharides from accumulating in the cytosol. Moreover, knockdown of sialin, a lysosomal transporter of sialic acids, resulted in a significant reduction of sialyloligosaccharides, implying that autophagy affects the substrate specificity of this transporter. This study thus provides a surprising link between basal autophagy and catabolism of N -linked glycans. Background: The role of autophagy in glycan catabolism remains to be clarified. Results: In Atg5 −/− cells, defective in autophagosome formation, sialyloligosaccharides accumulate specifically in the cytosol. Conclusion: Basal autophagy is essential for lysosomal catabolism of sialyloligosaccharides. Significance: This result not only underscores the importance of autophagy in glycan catabolism but also suggests that basal autophagy is required for proper function of lysosomes.