ERK-mediated phosphorylation of TFAM downregulates mitochondrial transcription: implications for Parkinson's disease.
Mitochondrion
; 17: 132-40, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24768991
ABSTRACT
Mitochondrial transcription factor A (TFAM) regulates mitochondrial biogenesis, which is downregulated by extracellular signal-regulated protein kinases (ERK1/2) in cells treated chronically with the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+). We utilized mass spectrometry to identify ERK1/2-dependent TFAM phosphorylation sites. Mutation of TFAM at serine 177 to mimic phosphorylation recapitulated the effects of MPP+ in decreasing the binding of TFAM to the light strand promoter, suppressing mitochondrial transcription. Mutant TFAM was unable to affect respiratory function or rescue the effects of MPP+ on respiratory complexes. These data disclose a novel mechanism by which ERK1/2 regulates mitochondrial function through direct phosphorylation of TFAM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Factores de Transcripción
/
Transcripción Genética
/
Regulación de la Expresión Génica
/
Proteínas Mitocondriales
/
Quinasas MAP Reguladas por Señal Extracelular
/
Proteínas de Unión al ADN
/
Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mitochondrion
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos