Monomethyl branched-chain fatty acid mediates amino acid sensing upstream of mTORC1.
Dev Cell
; 56(19): 2692-2702.e5, 2021 10 11.
Article
em En
| MEDLINE
| ID: mdl-34610328
ABSTRACT
Animals have developed various nutrient-sensing mechanisms for survival under fluctuating environmental conditions. Although extensive cell-culture-based analyses have identified diverse mediators of amino acid sensing upstream of mTOR, studies using animal models to examine intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here, we developed a Caenorhabditis elegans model to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid and its downstream metabolite, glycosphingolipid, which critically mediates the overall amino acid sensing by intestinal and neuronal mTORC1, which in turn regulates postembryonic development at least partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may operate in mammals. This study uncovers an amino-acid-sensing mechanism mediated by a lipid biosynthesis pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Graxos
/
Alvo Mecanístico do Complexo 1 de Rapamicina
/
Aminoácidos
Limite:
Animals
Idioma:
En
Revista:
Dev Cell
Ano de publicação:
2021
Tipo de documento:
Article