Milton/Trak 1/2 Protein and the Transport of Mitochondria

This project investigates the means by which mitochondria are moved within cells, particularly those of the nervous system. Building on our discovery of Milton as an essential protein in the axonal transport of mitochondria, these studies seek to determine both the biochemical mechanism of Milton action and its physiological role. We have described a protein complex composed of Milton, Miro, and Kinesin-1 Heavy Chain that functions as motor, adaptor, and regulator for moving mitochondria. We showed that Ca2+ regulation of this complex helps neurons survive excitotoxic insults, that PINK 1 and Parkin, two proteins whose genes are mutated in forms of Parkinson’s disease, interact with the complex and regulate mitochondrial motility, and most recently uncovered a mechanism by which extracellular glucose also regulates mitochondrial motility. We are continuing to examine that mechanism and its significance to the viability of neurons. Taken together, these studies should provide important insights into the cellular mechanisms that control mitochondrial motility, a critical process that acts to regulate multiple aspects of neuronal function and whose compromise can lead to neurodegeneration.  Most recently, we also discovered that mitochondria lose their motor proteins when a cell undergoes mitosis and this shedding of motors is crucial for insuring progression through the cell cycle and correct inheritance of mitochondria by daughter cells.