Discovery of a novel degradation mechanism for lipid-linked oligosaccharides

September 29, 2025

A step toward elucidating the full picture of n-linked glycan metabolism regulation

Researchers at RIKEN CSRS, together with colleagues from the RIKEN Pioneering Research Institute, the University of Tokyo, and the University of Toronto, have identified the gene encoding “DLO pyrophosphatase” (DLO-PP'ase), an enzyme involved in the degradation of dolichol-linked oligosaccharides (DLOs). DLOs are precursors of N-linked glycans attached to asparagine residues in proteins. Although DLO-PP'ase has been known to degrade accumulated DLO intermediates since 1974, its encoding gene had not been identified in any organism. While the biosynthetic pathway of DLOs is well understood, how their degradation is regulated under stress or environmental changes remains unclear.

In this study, the international team identified the DLO-PP'ase gene in the budding yeast, Saccharomyces cerevisiae, naming it LLP1. The LLP1 gene product is conserved among fungi, yeasts, and some bacteria, in which its homolog is VanZ—a gene of unknown function linked to vancomycin resistance. LLP1 localizes to the Golgi apparatus, and its deletion leads to the accumulation of DLOs with abnormal glycan structures, indicating its key role in DLO homeostasis and quality control. This discovery of a novel catabolic mechanism for lipid-linked oligosaccharides is expected to advance our understanding of glycan metabolic regulation. Notably, no homologous gene has been found in mammals, including humans, and the team is now working to identify the human DLO-PP'ase gene.

 

Original article

Journal of Cell Biology　doi: 10.1083/jcb.202501239

S.-T. Li, K. Kamada, A. Honda, J. Seino, T. Matsuda, T. Suzuki, N. Dohmae, Y. Shichino, S. Iwasaki, Y. Noda, . Costanzo, C. Boone, T. Suzuki,

"LLP1 is a pyrophosphatase involved in homeostasis/quality control of dolichol-linked oligosaccharide".

Contact

Naoshi Dohmae
Unit Leader
Biomolecular Characterization Unit