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. Continuing the project, we will investigate whether this complex functions exclusively in anterograde transport or also is needed for retrograde mitochondrial transport and the movement of mitochondria within neuronal cell bodies. We are examining the mechanism by which mitochondrial movements are regulated by Ca++ and by metabolites. We will also examine whether mitochondrial proteins linked to Parkinsonism will regulate mitochondrial motility and distribution.To these ends, we will further characterize the association of Milton with known protein partners and seek to identify other novel protein interactors. 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.
