mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation.
Cell Metab
; 18(5): 698-711, 2013 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-24206664
ABSTRACT
mRNA translation is thought to be the most energy-consuming process in the cell. Translation and energy metabolism are dysregulated in a variety of diseases including cancer, diabetes, and heart disease. However, the mechanisms that coordinate translation and energy metabolism in mammals remain largely unknown. The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates mRNA translation and other anabolic processes. We demonstrate that mTORC1 controls mitochondrial activity and biogenesis by selectively promoting translation of nucleus-encoded mitochondria-related mRNAs via inhibition of the eukaryotic translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs). Stimulating the translation of nucleus-encoded mitochondria-related mRNAs engenders an increase in ATP production capacity, a required energy source for translation. These findings establish a feed-forward loop that links mRNA translation to oxidative phosphorylation, thereby providing a key mechanism linking aberrant mTOR signaling to conditions of abnormal cellular energy metabolism such as neoplasia and insulin resistance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Biossíntese de Proteínas
/
Regulação da Expressão Gênica
/
Fatores de Iniciação em Eucariotos
/
Complexos Multiproteicos
/
Proteínas Adaptadoras de Transdução de Sinal
/
Serina-Treonina Quinases TOR
/
Renovação Mitocondrial
/
Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Metab
Assunto da revista:
METABOLISMO
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Canadá