Parkin R274W mutation affects muscle physiology via the PARIS-PGC-1α pathway
Recessive mutations in the Parkin gene (PRKN) are the most common cause of young-onset inherited parkinsonism. Parkin is a multifunctional E3 ubiquitin ligase that plays a variety of roles in the cell including the degradation of proteins and the maintenance of mitochondrial homeostasis, integrity, and biogenesis via the PARIS-PGC-1 pathway. In 2001 the R275W mutation in the PRKN gene was identified in two unrelated families with a multigenerational history of postural tremor, dystonia and parkinsonism. Drosophila models of Parkin R275W showed selective and progressive degeneration of dopaminergic neuronal clusters, mitochondrial abnormalities, and prominent climbing defects. In the Prkn mouse orthologue, the amino acid R274 corresponds to human R275. Here we described a muscle phenotype in R274W +/+ mice and discovered that a defective Parkin-PARIS-PGC-1 pathway may impact mitochondrial biogenesis and, eventually, myoblast proliferation and differentiation.