ArticleProceedings of the National Academy of Sciences of the United States of America2013
Metabolically programmed quality control system for dolichol-linked oligosaccharides.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Mannose metabolic pathway senses glucose supply and regulates cell fate decisions.The Journal of biological chemistry · 2026Article
- Tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation.Cell death & disease · 2024Article
- Metabolic clogging of mannose triggers dNTP loss and genomic instability in human cancer cells.eLife · 2023Article
- The hexosamine pathway and coat complex II promote malignant adaptation to nutrient scarcity.Life science alliance · 2022Article
- Dynamic tracing of sugar metabolism reveals the mechanisms of action of synthetic sugar analogs.Glycobiology · 2022Article
- Topological and enzymatic analysis of human Alg2 mannosyltransferase reveals its role in lipid-linked oligosaccharide biosynthetic pathway.Communications biology · 2022Article
- Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis.Nature structural & molecular biology · 2021Article
- Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.STAR protocols · 2021Article
- Disruption of Endoplasmic Reticulum Proteostasis in Age-Related Nervous System Disorders.Progress in molecular and subcellular biology · 2021Article
- Toolbox Accelerating Glycomics (TAG): Glycan Annotation from MALDI-TOF MS Spectra and Mapping Expression Variation to Biosynthetic Pathways.Biomolecules · 2020Article
- β-Oxidation and autophagy are critical energy providers during acute glucose depletion in SProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Bacterial Lipid II Analogs: Novel In Vitro Substrates for Mammalian Oligosaccharyl Diphosphodolichol Diphosphatase (DLODP) Activities.Molecules (Basel, Switzerland) · 2019Article
- Transcriptional analysis of Foxp3+ Tregs and functions of two identified molecules during resolution of ALI.JCI insight · 2019Article
- Brefeldin A promotes the appearance of oligosaccharyl phosphates derived from Glc3Man9GlcNAc2-PP-dolichol within the endomembrane system of HepG2 cells.Journal of lipid research · 2016Article
- Demonstration of an oligosaccharide-diphosphodolichol diphosphatase activity whose subcellular localization is different than those of dolichyl-phosphate-dependent enzymes of the dolichol cycle.Journal of lipid research · 2016Article
- Non-lysosomal Degradation of Singly Phosphorylated Oligosaccharides Initiated by the Action of a Cytosolic Endo-β-N-acetylglucosaminidase.The Journal of biological chemistry · 2016Article
- Article
- Generation and degradation of free asparagine-linked glycans.Cellular and molecular life sciences : CMLS · 2015Review
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Authors and funding
7 authors.
Funding
Abstract
The glycolipid Glc3Man9GlcNAc2-pyrophosphate-dolichol serves as the precursor for asparagine (N)-linked protein glycosylation in mammals. The biosynthesis of dolichol-linked oligosaccharides (DLOs) is arrested in low-glucose environments via unknown mechanisms, resulting in abnormal N-glycosylation. Here, we show that under glucose deprivation, DLOs are prematurely degraded during the early stages of DLO biosynthesis by pyrophosphatase, leading to the release of singly phosphorylated oligosaccharides into the cytosol. We identified that the level of GDP-mannose (Man), which serves as a donor substrate for DLO biosynthesis, is substantially reduced under glucose deprivation. We provide evidence that the selective shutdown of the GDP-Man biosynthetic pathway is sufficient to induce the release of phosphorylated oligosaccharides. These results indicate that glucose-regulated metabolic changes in the GDP-Man biosynthetic pathway cause the biosynthetic arrest of DLOs and facilitate their premature degradation by pyrophosphatase. We propose that this degradation system may avoid abnormal N-glycosylation with premature oligosaccharides under conditions that impair efficient DLO biosynthesis.
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