Role of pink1, a Parkinson related gene, in mitochondria and synaptic activity.

Mitochondria are dynamic organelles involved in ATP production, buffering of calcium and apoptosis. Genetic studies of neuromuscular junctions in Drosophila have demonstrated that synapses without mitochondria show defects in the mobilization of a reserve pool (RP) of vesicles. These defects are ATP dependent. Mutants of pink1, a gene involved in inherited Parkinsons disease (PD), also display an RP defect. This defect is probably caused by a depolarization of the mitochondrial membrane, caused by a decreased Complex I function, which leads to a reduction of the oxidative phosphorylation. With the proposed project we want to gain further insight in the role of pink1 in synaptic mitochondria, and better understand the etiology of PD. Two approaches will be used to do this: 1) understand how Pink1 interacts with Complex I. To check whether Complex I is the direct and most important target of Pink1, a functional rescue of pink1 with yeast Complex I will be performed. We will use RNAi against all the nuclear encoding subunits of Complex I in order to show which subunit is affected by Pink1. 2) We are performing a genetic screen to find novel genes that, on one hand, are dominant suppressors of pink1 mutant phenotypes and, on the other hand, play a role in neuronal communication.

Keywords:Parkinson's disease, Pink1, Drosophila, Neuronal communication, Mitochondria, Complex I

Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing, Microbiology