Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy.
Mol Cell
; 43(4): 572-85, 2011 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-21855797
ABSTRACT
Autophagy, the primary recycling pathway of cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the response to cellular stress. The Hsp90-Cdc37 chaperone complex coordinately regulates the activity of select kinases to orchestrate many facets of the stress response. Although both maintain mitochondrial integrity, the relationship between Hsp90-Cdc37 and autophagy has not been well characterized. Ulk1, one of the mammalian homologs of yeast Atg1, is a serine-threonine kinase required for mitophagy. Here we show that the interaction between Ulk1 and Hsp90-Cdc37 stabilizes and activates Ulk1, which in turn is required for the phosphorylation and release of Atg13 from Ulk1, and for the recruitment of Atg13 to damaged mitochondria. Hsp90-Cdc37, Ulk1, and Atg13 phosphorylation are all required for efficient mitochondrial clearance. These findings establish a direct pathway that integrates Ulk1- and Atg13-directed mitophagy with the stress response coordinated by Hsp90 and Cdc37.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Choque Térmico HSP90
/
Chaperoninas
/
Proteínas de Ciclo Celular
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas Adaptadoras de Transdução de Sinal
/
Mitocôndrias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos