Mutations of parkin, an E3 ubiquitin ligase in the ubiquitin proteasomal system (UPS), cause autosomal recessive juvenile Parkinson’s disease (ARJ-PD). Parkin protects against dopaminergic neuronal cell death induced by a number of cellular insults. Although mainly localized to the cytoplasm, parkin has been reported to involve in the maintenance of mitochondrial morphology and function, with the detailed mechanism remained unknown. In this study, we identified a novel interacting protein of parkin, called p32. Previous studies have found that p32 is localized to the mitochondria and is an important protein in regulating mitochondrial ATP generation and mitochondrial dependent cell death. We discovered that p32 functioned upstream of parkin, and it regulated parkin’s level...[ Read more ]

Mutations of parkin, an E3 ubiquitin ligase in the ubiquitin proteasomal system (UPS), cause autosomal recessive juvenile Parkinson’s disease (ARJ-PD). Parkin protects against dopaminergic neuronal cell death induced by a number of cellular insults. Although mainly localized to the cytoplasm, parkin has been reported to involve in the maintenance of mitochondrial morphology and function, with the detailed mechanism remained unknown. In this study, we identified a novel interacting protein of parkin, called p32. Previous studies have found that p32 is localized to the mitochondria and is an important protein in regulating mitochondrial ATP generation and mitochondrial dependent cell death. We discovered that p32 functioned upstream of parkin, and it regulated parkin’s level by controlling parkin’s degradation through autophagy pathway. We further demonstrated that p32/parkin pathway controlled mitochondrial morphology and motility. This study provides new insights into the role of parkin in the mitochondrial dynamics and function.