Parkinson’s Disease (PD) is the common neurodegeneration disease characterized by dopaminergic neurons death in substantia nigra. The typical hallmark is the built-up Lewy bodies which are abnormal aggregates of protein in the neurons. Mutations in parkin are the second most common known cause of PD. Loss of parkin, an E3 ubiquitin ligase, is thought to play a pathogenic role not only in autosomal recessive Familial PD but also in sporadic PD; It is postulated that loss of its E3 ubiquitin ligase function may disrupt the ubiquitin-mediated protein degradation which may cause abnormal protein aggregation; However, few cases with Lewy bodies, the typical hallmarks of PD, were observed in the PD patients with parkin mutations. The association of parkin deficiency with dysfunctional...[ Read more ]

Parkinson’s Disease (PD) is the common neurodegeneration disease characterized by dopaminergic neurons death in substantia nigra. The typical hallmark is the built-up Lewy bodies which are abnormal aggregates of protein in the neurons. Mutations in parkin are the second most common known cause of PD. Loss of parkin, an E3 ubiquitin ligase, is thought to play a pathogenic role not only in autosomal recessive Familial PD but also in sporadic PD; It is postulated that loss of its E3 ubiquitin ligase function may disrupt the ubiquitin-mediated protein degradation which may cause abnormal protein aggregation; However, few cases with Lewy bodies, the typical hallmarks of PD, were observed in the PD patients with parkin mutations. The association of parkin deficiency with dysfunctional mitochondria was raised from the pioneering research in Drosophila model. Later, numerous studies have showed that parkin together with PINK1 is involved in the mitophagy in mammalian cells. Mitophagy is an autophagic process to selectively degrade damaged mitochondria which aims to maintain normal mitochondrial functions in cell and had been suggested to play a vital role in regulating neuronal survival in the pathogenesis of PD. Our previous study had identified a mitochondrial protein p32 as a novel parkin interactor. Nonetheless, the role of p32 involved in mitophagy remains unknown. In this study, p32 knock out neuroblastoma cell line SH-SY5Y was established by CRISPR/Cas9. We found that p32 played a role in regulating mitochondrial morphology and dynamics identical to previous study. The mitochondrial content proteins were significantly less in p32 KO cell line than in WT. The p32 interacting with parkin in mitophagy still needs to be furtherly investigated, which may provide a new insight and potential direction in PD research.