Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions.

Détails

Ressource 1Télécharger: Nature_Metabolism2023.pdf (9135.49 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_A1A6C5A94F05
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions.
Périodique
Nature metabolism
Auteur⸱e⸱s
Skinner O.S., Blanco-Fernández J., Goodman R.P., Kawakami A., Shen H., Kemény L.V., Joesch-Cohen L., Rees M.G., Roth J.A., Fisher D.E., Mootha V.K., Jourdain A.A.
ISSN
2522-5812 (Electronic)
ISSN-L
2522-5812
Statut éditorial
Publié
Date de publication
17/05/2023
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized genome-wide genetic screens and a PRISM growth assay across 482 cancer cell lines. We report that catabolism of uridine from the medium enables the growth of cells in the complete absence of glucose. While previous studies have shown that uridine can be salvaged to support pyrimidine synthesis in the setting of mitochondrial oxidative phosphorylation deficiency <sup>1</sup> , our work demonstrates that the ribose moiety of uridine or RNA can be salvaged to fulfil energy requirements via a pathway based on: (1) the phosphorylytic cleavage of uridine by uridine phosphorylase UPP1/UPP2 into uracil and ribose-1-phosphate (R1P), (2) the conversion of uridine-derived R1P into fructose-6-P and glyceraldehyde-3-P by the non-oxidative branch of the pentose phosphate pathway and (3) their glycolytic utilization to fuel ATP production, biosynthesis and gluconeogenesis. Capacity for glycolysis from uridine-derived ribose appears widespread, and we confirm its activity in cancer lineages, primary macrophages and mice in vivo. An interesting property of this pathway is that R1P enters downstream of the initial, highly regulated steps of glucose transport and upper glycolysis. We anticipate that 'uridine bypass' of upper glycolysis could be important in the context of disease and even exploited for therapeutic purposes.
Pubmed
Open Access
Oui
Financement(s)
Fonds national suisse / Projets / 310030_200796
Création de la notice
23/05/2023 12:55
Dernière modification de la notice
27/05/2023 5:50
Données d'usage