Metabolically programmed quality control system for dolichol-linked oligosaccharides

In mammals, asparagine (N)-linked glycosylation of nascent polypeptides synthesized in the endoplasmic reticulum regulates folding, degradation, and intracellular trafficking of the glycoproteins. The normal N-glycosylation requires the completely-assembled dolichol-linked oligosaccharide (DLO) as the optimal glycan donor substrate; however, a low-glucose environment causes arrest of the DLO assembly, which results in the synthesis of extensively truncated premature DLOs, thereby increasing a risk of abnormal N-glycosylation. Here, we report that under low-glucose conditions, the premature DLOs are efficiently degraded by unidentified pyrophosphatase, catabolizing them to singly phosphorylated oligosaccharides. Our results suggest that the pyrophosphatase-mediated degradation of premature DLOs functions as a quality control system to avoid abnormal N-glycosylation under conditions that impair efficient DLO biosynthesis.