Deficit in PINK1/PARKIN-mediated mitochondrial autophagy at late stages of dystrophic cardiomyopathy.
Cardiovasc Res
; 114(1): 90-102, 2018 01 01.
Article
en En
| MEDLINE
| ID: mdl-29036556
ABSTRACT
Aims:
Duchenne muscular dystrophy (DMD) is an inherited devastating muscle disease with severe and often lethal cardiac complications. Emerging evidence suggests that the evolution of the pathology in DMD is accompanied by the accumulation of mitochondria with defective structure and function. Here, we investigate whether defects in the housekeeping autophagic pathway contribute to mitochondrial and metabolic dysfunctions in dystrophic cardiomyopathy. Methods andresults:
We employed various biochemical and imaging techniques to assess mitochondrial structure and function as well as to evaluate autophagy, and specific mitochondrial autophagy (mitophagy), in hearts of mdx mice, an animal model of DMD. Our results indicate substantial structural damage of mitochondria and a significant decrease in ATP production in hearts of mdx animals, which developed cardiomyopathy. In these hearts, we also detected enhanced autophagy but paradoxically, mitophagy appeared to be suppressed. In addition, we found decreased levels of several proteins involved in the PINK1/PARKIN mitophagy pathway as well as an insignificant amount of PARKIN protein phosphorylation at the S65 residue upon induction of mitophagy.Conclusions:
Our results suggest faulty mitophagy in dystrophic hearts due to defects in the PINK1/PARKIN pathway.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Autofagia
/
Distrofia Muscular de Duchenne
/
Miocitos Cardíacos
/
Ubiquitina-Proteína Ligasas
/
Mitofagia
/
Mitocondrias Cardíacas
/
Cardiomiopatías
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos