Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy.
Biochim Biophys Acta
; 1852(1): 12-21, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25446991
ABSTRACT
The G2019S leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic Parkinson's disease (PD). However, the molecular mechanism underlying LRRK2 G2019S-induced cellular pathology is poorly understood. Here, we demonstrated that LRRK2 G2019S bound to and phosphorylated Bcl-2, a mitochondrial anti-apoptotic protein, at Threonine 56. Either stable expression of Bcl-2 or transient expression of a Bcl-2 phosphor mutant (Bcl-2(T56A)) abolished LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Together, our findings reveal a previously unidentified target of LRRK2 G2019S, showing that Bcl-2 serves as a point of crosstalk between LRRK2 G2019S-mediated mitochondrial disorder and dysregulation of autophagy.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autofagia
/
Treonina
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Proteínas Serina-Treonina Quinasas
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Proteínas Proto-Oncogénicas c-bcl-2
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Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos