Hexosamine pathway metabolites enhance protein quality control and prolong life.
Cell
; 156(6): 1167-1178, 2014 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-24630720
ABSTRACT
Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Vias Biossintéticas
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Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)
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Hexosaminas
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Longevidade
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha