Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments.
EMBO J
; 34(18): 2334-49, 2015 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-26228940
ABSTRACT
The cellular proteostasis network integrates the protein folding and clearance machineries in multiple sub-cellular compartments of the eukaryotic cell. The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. A distinctive feature of the ER is its tightly controlled redox homeostasis necessary for the formation of inter- and intra-molecular disulphide bonds. Employing genetically encoded in vivo sensors reporting on the redox state in an organelle-specific manner, we show in the nematode Caenorhabditis elegans that the redox state of the ER is subject to profound changes during worm lifetime. In young animals, the ER is oxidizing and this shifts towards reducing conditions during ageing, whereas in the cytosol the redox state becomes more oxidizing with age. Likewise, the redox state in the cytosol and the ER change in an opposing manner in response to proteotoxic challenges in C. elegans and in HeLa cells revealing conservation of redox homeostasis. Moreover, we show that organelle redox homeostasis is regulated across tissues within C. elegans providing a new measure for organismal fitness.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Caenorhabditis elegans
/
Retículo Endoplasmático
/
Deficiências na Proteostase
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article