Non-lysosomal degradation pathway for N-linked glycans and dolichol-linked oligosaccharides

•fOSs and POSs are liberated from dolichol-linked oligosaccharides at the ER membrane.•The cytosol is a site for deglycosylation of misfolded N-glycoproteins.•These novel pathways constitute the so-called “non-lysosomal” degradation pathway for glycans. There is growing evidence that asparagine (N)-linked glycans play pivotal roles in protein folding and intra- or intercellular trafficking of N-glycosylated proteins. During the N-glycosylation of proteins, significant amounts of free oligosaccharides (fOSs) and phosphorylated oligosaccharides (POSs) are generated at the endoplasmic reticulum (ER) membrane by unclarified mechanisms. fOSs are also formed in the cytosol by the enzymatic deglycosylation of misfolded glycoproteins destined for proteasomal degradation. This article summarizes the current knowledge of the molecular and regulatory mechanisms underlying the formation of fOSs and POSs in mammalian cells and Saccharomyces cerevisiae.