The conserved NUS-1/DHDDS-1 complex links N-glycosylation to lipid and lysosomal homeostasis in C. elegans.

Loss of NUS-1/DHDDS-1 in C. elegans disrupts N-glycosylation, causing ER stress, lysosomal collapse, and systemic lipopenia, linking glycosylation to lipid and lysosomal homeostasis.

• Why it matters: Understanding how protein glycosylation influences systemic lipid and lysosomal functions addresses gaps in knowledge about the mechanisms underlying congenital disorders of glycosylation (CDG) and their systemic effects.
• What they did: The study used C. elegans to show that the cis-prenyltransferase complex interacts with the OST complex to regulate N-glycan transfer, and that loss of NUS-1/DHDDS-1 impairs glycosylation of SCAP, leading to its degradation and lipid synthesis failure.
• The result: These findings reveal a mechanistic link between N-glycosylation and lipid metabolism, providing insights into the systemic pathophysiology of CDG and potential targets for therapeutic intervention.