The role of parkin-picki in mithchondrial dysfunction

Abstract

Autosomal Recessive Juvenile Parkinsonism (ARJP) is the most common motor-related neurodegenerative disease, which occurs in young adults between 20-40 years of age. Mutations in the parkin (PARK2) gene are associated ARJP, which result in the loss of dopaminergic neurons of substantia nigra pars compacta in the mid brain. Parkin, an E3 ligase, is an enzyme responsible for ubiquitination of several proteins leading to their degradation in Ubiquitin Proteasomal System (UPS) and promoting autophagy of depolarized mitochondria. Mutations in the parkin gene are thought to result in protein aggregation of parkin substrates resulting in neuronal toxicity. Among these parkin interacting proteins and substrates, several play important roles in mitochondrial function, oxidative stress, cellular toxicity and apoptosis. This project focused on investigating the role of one particular protein that interacts with parkin, namely, PICK1. Specifically, the studies herein investigated the role of a parkin-PICK1 interaction in mitochondrial function and oxidative stress.