Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1.
J Neurochem
; 118(4): 636-45, 2011 Aug.
Article
en En
| MEDLINE
| ID: mdl-21615408
ABSTRACT
Mutations in the parkin gene cause early-onset, autosomal recessive Parkinson's disease. Parkin functions as an E3 ubiquitin ligase to mediate the covalent attachment of ubiquitin monomers or linked chains to protein substrates. Substrate ubiquitination can target proteins for proteasomal degradation or can mediate a number of non-degradative functions. Parkin has been shown to preserve mitochondrial integrity in a number of experimental systems through the regulation of mitochondrial fission. Upon mitochondrial damage, parkin translocates to mitochondria to mediate their selective elimination by autophagic degradation. The mechanism underlying this process remains unclear. Here, we demonstrate that parkin interacts with and selectively mediates the atypical poly-ubiquitination of the mitochondrial fusion factor, mitofusin 1, leading to its enhanced turnover by proteasomal degradation. Our data supports a model whereby the translocation of parkin to damaged mitochondria induces the degradation of mitofusins leading to impaired mitochondrial fusion. This process may serve to selectively isolate damaged mitochondria for their removal by autophagy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Membrana
/
Proteínas Mitocondriales
/
Ubiquitina-Proteína Ligasas
/
Ubiquitinación
/
GTP Fosfohidrolasas
/
Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Neurochem
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suiza