Phospholipase D-dependent mTOR complex 1 (mTORC1) activation by glutamine.
J Biol Chem
; 293(42): 16390-16401, 2018 10 19.
Article
em En
| MEDLINE
| ID: mdl-30194281
ABSTRACT
Glutamine is a key nutrient required for sustaining cell proliferation, contributing to nucleotide, protein, and lipid synthesis. The mTOR complex 1 (mTORC1) is a highly conserved protein complex that acts as a sensor of nutrients, relaying signals for the shift from catabolic to anabolic metabolism. Although glutamine plays an important role in mTORC1 activation, the mechanism is not clear. Here we describe a leucine- and Rag-independent mechanism of mTORC1 activation by glutamine that depends on phospholipase D and the production of phosphatidic acid, which is required for the stability and activity of mTORC1. The phospholipase D-dependent activation of mTORC1 by glutamine depended on the GTPases ADP ribosylation factor 1 (Arf1), RalA, and Rheb. Glutamine deprivation could be rescued by α-ketoglutarate, a downstream metabolite of glutamine. This mechanism represents a distinct nutrient input to mTORC1 that is independent of Rag GTPases and leucine.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipase D
/
Alvo Mecanístico do Complexo 1 de Rapamicina
/
Glutamina
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2018
Tipo de documento:
Article