Stress-regulated translational attenuation adapts mitochondrial protein import through Tim17A degradation.
Cell Metab
; 18(6): 908-19, 2013 Dec 03.
Article
en En
| MEDLINE
| ID: mdl-24315374
ABSTRACT
Stress-regulated signaling pathways protect mitochondrial proteostasis and function from pathologic insults. Despite the importance of stress-regulated signaling pathways in mitochondrial proteome maintenance, the molecular mechanisms by which these pathways maintain mitochondrial proteostasis remain largely unknown. We identify Tim17A as a stress-regulated subunit of the translocase of the inner membrane 23 (TIM23) mitochondrial protein import complex. We show that Tim17A protein levels are decreased downstream of stress-regulated translational attenuation induced by eukaryotic initiation factor 2α (eIF2α) phosphorylation through a mechanism dependent on the mitochondrial protease YME1L. Furthermore, we demonstrate that decreasing Tim17A attenuates TIM23-dependent protein import, promotes the induction of mitochondrial unfolded protein response (UPR)-associated proteostasis genes, and confers stress resistance in C. elegans and mammalian cells. Thus, our results indicate that Tim17A degradation is a stress-responsive mechanism by which cells adapt mitochondrial protein import efficiency and promote mitochondrial proteostasis in response to the numerous pathologic insults that induce stress-regulated translation attenuation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Estrés Oxidativo
/
Proteínas de Transporte de Membrana Mitocondrial
/
Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2013
Tipo del documento:
Article