son's disease is a neurodegenerative disease characterized by tremors, muscle stiffness, and muscle weakness. Molecular genetic analysis has confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated with Parkinson's disease. PARKIN is an E3 ubiquitin ligase that translocates to mitochondria during loss of mitochondrial membrane potential to increase mitophagy. Although muscle dysfunction is noted in

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... son's disease, little is known about the involvement of PARKIN in the muscle phenotype of Parkinson's disease. In this study, we report that the mitochondrial uncoupler CCCP promotes PINK1/PARKIN-mediated mitophagy in myogenic C2C12 cells. As a result of this excess mitophagy, we show that CCCP treatment of myotubes leads to the development of myotube atrophy in vitro. Surprisingly, we also found that siRNA-mediated knockdown of Parkin results in impaired mitochondrial turnover. In addition, knockdown of Parkin 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. atrophy; mitochondria; mitochondrial turnover; Parkin; skeletal muscle * C. McFarlane and R. Kambadur are co-senior authors.