Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
J Cell Biol ; 217(2): 635-647, 2018 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-29187525

RESUMEN

Chaperone-mediated autophagy (CMA) serves as quality control during stress conditions through selective degradation of cytosolic proteins in lysosomes. Humanin (HN) is a mitochondria-associated peptide that offers cytoprotective, cardioprotective, and neuroprotective effects in vivo and in vitro. In this study, we demonstrate that HN directly activates CMA by increasing substrate binding and translocation into lysosomes. The potent HN analogue HNG protects from stressor-induced cell death in fibroblasts, cardiomyoblasts, neuronal cells, and primary cardiomyocytes. The protective effects are lost in CMA-deficient cells, suggesting that they are mediated through the activation of CMA. We identified that a fraction of endogenous HN is present at the cytosolic side of the lysosomal membrane, where it interacts with heat shock protein 90 (HSP90) and stabilizes binding of this chaperone to CMA substrates as they bind to the membrane. Inhibition of HSP90 blocks the effect of HNG on substrate translocation and abolishes the cytoprotective effects. Our study provides a novel mechanism by which HN exerts its cardioprotective and neuroprotective effects.


Asunto(s)
Autofagia , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Chaperonas Moleculares/metabolismo , Animales , Supervivencia Celular , Células Cultivadas , Citosol/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Lisosomas/metabolismo , Masculino , Ratones , Células 3T3 NIH , Ratas , Ratas Wistar
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA