Role of mitophagy in muscle growth and metabolism

Abstract

Parkinson’s Disease (PD) is a neurodegenerative disease characterized by tremors, muscle stiffness and muscle weakness. Molecular genetic analysis confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated with PD. Although muscle dysfunction is noted in PD, little is known about the involvement of PARKIN in the muscle phenotype of PD. In this study, results show that the mitochondrial uncoupler CCCP promotes PINK1/PARKIN-mediated mitophagy in myogenic C2C12 cells. As a result of this excess mitophagy, CCCP treatment of myotubes leads to the development of myotube atrophy in vitro. Surprisingly, siRNA-mediated knock down of Parkin results in accumulation of dysfunctional mitochondria. In addition, knock down of Parkin also led to myotubular atrophy in vitro. Consistent with these in vitro results, Parkin knockout muscles showed impaired mitochondrial function and smaller myofiber area, suggesting that Parkin function is required for post-natal skeletal muscle growth and development. These findings open new perspectives through investigation of PD from skeletal muscle angle, and may lead to discovery of new therapeutic targets for the treatment of PD.