Temporal orchestration of circadian autophagy rhythm by C/EBPß.
EMBO J
; 30(22): 4642-51, 2011 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-21897364
ABSTRACT
Temporal organization of tissue metabolism is important for maintaining nutrient and energy homeostasis in mammals. Autophagy is a conserved cellular pathway that is activated in response to nutrient limitation, resulting in the degradation of cytoplasmic components and the release of amino acids and other nutrients. Here, we show that autophagy exhibits robust circadian rhythm in mouse liver, which is accompanied by cyclic induction of genes involved in various steps of autophagy. Functional analyses of transcription factors and cofactors identified C/EBPß as a potent activator of autophagy. C/EBPß is rhythmically expressed in the liver and is regulated by both circadian and nutritional signals. In cultured primary hepatocytes, C/EBPß stimulates the program of autophagy gene expression and is sufficient to activate autophagic protein degradation. Adenoviral-mediated RNAi knockdown of C/EBPß in vivo abolishes diurnal autophagy rhythm in the liver. Further, circadian regulation of C/EBPß and autophagy is disrupted in mice lacking a functional liver clock. We have thus identified C/EBPß as a key factor that links autophagy to biological clock and maintains nutrient homeostasis throughout light/dark cycles.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Ritmo Circadiano
/
Proteína beta Intensificadora de Ligação a CCAAT
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos