Mitochondrial Trafficking in Dopaminergic Neuron Injury

Mitochondria are considered to be the "power house" of all cells, including neurons, because they convert food into energy in the form that cells can use. When mitochondria fail, cells typically die because this supply of energy is essential for maintaining cell viability. Recent studies have shown that mitochondria in dopaminergic neurons are especially vulnerable to injury, so that mitochondrial failure may be a proximate cause of Parkinson's disease. Although neurons rarely divide and replicate, mitochondria are continuously produced within neurons, and newly born mitochondria then have to travel to distant parts of the neuron in order to provide a local supply of energy. The main theory to be tested in this project is that injury and death of dopaminergic neurons is a consequence of the failure of new mitochondria to be delivered to the appropriate parts of the neuron, with the consequence that the neuron is locally starved of energy. We will test the theory by using a brain slice preparation cultured in vitro. Using a variety of molecular approaches, we will introduce fluorescent proteins into mitochondria in dopaminergic neurons. We will then track the movement of the mitochondria in healthy and injured dopaminergic neurons. These studies will hopefully provide the first examples of mitochondrial trafficking in a specific neuronal pathway, and may also provide insights into the mechanisms of dopaminergic neuron death relevant to the pathology of PD.