Beneficial effects of Glc-1,6-P2 modulation on mutant phosphomannomutase-2

IF 4.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-03-30 DOI:10.1016/j.bbamcr.2025.119948

Maria Monticelli , Debora Paris , Maria Chiara Monti , Elva Morretta , Zuzana Pakanova , Marek Nemcovic , Rebeka Kodrikova , Maria Vittoria Cubellis , Giuseppina Andreotti

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引用次数: 0

Abstract

The metabolite Glucose-1,6-bisphosphate (Glc-1,6-P₂) plays a vital role in human metabolism, and is a crucial activator and stabilizer for phosphomannomutase-2 (PMM2) - mutations within this protein propagate the most common congenital disorder of glycosylation (PMM2-CDG). In vivo, Glc-1,6-P₂ is hydrolysed by phosphomannomutase-1 (PMM1), predominantly in the brain, under the influence of inosine monophosphate (IMP). In the present study, we employed knock-out PMM1 in ^{Arg141His/Phe119Leu}PMM2 patient-derived fibroblasts and investigated the phenotypic improvement. Increased Glc-1,6-P₂ was associated with glycosylation enhancement, confirmed by glycan profiling. Previously identified PMM2-CDG biomarkers, such as LAMP1, PTX3 and lysosomal enzymes showed empirical imrovement- these findings were corroborated by metabolomic and proteomic analysis. Moreover, our results support the potential of Glc-1,6-P₂ modulation for PMM2-CDG, potentiating novel perspectives in drug discovery.

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来源期刊

Biochimica et biophysica acta. Molecular cell research 生物-生化与分子生物学

CiteScore

10.00

自引率

2.00%

发文量

151

审稿时长

44 days

期刊介绍： BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.