Deficit in PINK1/PARKIN-mediated mitochondrial autophagy at late stages of dystrophic cardiomyopathy
| Autor: | Eeva-Liisa Eskelinen, Natalia Shirokova, Viktoriia Kyrychenko, Myriam A. Badr, Chifei Kang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Physiology Duchenne muscular dystrophy Ubiquitin-Protein Ligases Cardiomyopathy PINK1 Mitochondrion Biology Parkin Mitochondria Heart 03 medical and health sciences 0302 clinical medicine Adenosine Triphosphate Physiology (medical) Mitophagy medicine Autophagy Animals Myocytes Cardiac Phosphorylation Cellular Senescence Genetics Original Articles medicine.disease 3. Good health Cell biology Muscular Dystrophy Duchenne Disease Models Animal 030104 developmental biology biology.protein Mice Inbred mdx Cardiology and Cardiovascular Medicine Dystrophin Cardiomyopathies Microtubule-Associated Proteins Protein Kinases 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cardiovascular research. 114(1) |
| ISSN: | 1755-3245 |
| Popis: | 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 and results 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. |
| Databáze: | OpenAIRE |
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