Post-translational control of mitochondria by the ubiquitin ligase FBXO7

Parkinson's disease (PD) is the second most prevalent form of neurodegeneration, occurring in approximately 1% of people over the age of 60. Pathologically, the disease is characterized by a loss of dopaminergic neurons within the substantia nigra (SN), resulting in a depletion of dopamine levels. Mitochondrial dysfunctions are believed to play a key role in the development of PD, with many of the genes involved in the development of early onset forms of the disease being important in the regulation of mitochondrial function. Recently, mutations in the E3 ligase subunit Fbxo7 have been identified as causing familial Parkinsonism in a number of patients. Fbxo7 has also been linked to the maintenance of normal mitochondrial function, with mutations in the protein being associated with defects in mitophagy, increased mitochondrial protein aggregation and impaired metabolic function; processes which are likely to be of importance in the development of PD. The aims of this project are to gain a better understanding of the role which Fbxo7 plays in the regulation of mitochondria and how dysfunctions in these processes contribute to the development of PD.