Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS.

Détails

ID Serval
serval:BIB_B6C4CA41CF54
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS.
Périodique
Molecular cell
Auteur(s)
Jourdain A.A., Begg B.E., Mick E., Shah H., Calvo S.E., Skinner O.S., Sharma R., Blue S.M., Yeo G.W., Burge C.B., Mootha V.K.
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Statut éditorial
Publié
Date de publication
06/05/2021
Peer-reviewed
Oui
Volume
81
Numéro
9
Pages
1905-1919.e12
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Résumé
Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to disease. At present, the full set of molecular mechanisms governing the relative expression and balance of these two pathways is unknown. Here, we focus on genes whose loss leads to an increase in OXPHOS activity. Unexpectedly, this class of genes is enriched for components of the pre-mRNA splicing machinery, in particular for subunits of the U1 snRNP. Among them, we show that LUC7L2 represses OXPHOS and promotes glycolysis by multiple mechanisms, including (1) splicing of the glycolytic enzyme PFKM to suppress glycogen synthesis, (2) splicing of the cystine/glutamate antiporter SLC7A11 (xCT) to suppress glutamate oxidation, and (3) secondary repression of mitochondrial respiratory supercomplex formation. Our results connect LUC7L2 expression and, more generally, the U1 snRNP to cellular energy metabolism.
Mots-clé
7q-, LUC7, MDS, Tarui disease, cancer, ferroptosis, myelodysplastic syndrome, phosphofructokinase, spliceosome, system X(c)(−)
Pubmed
Web of science
Création de la notice
16/04/2021 10:20
Dernière modification de la notice
05/06/2021 6:33
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