Role of mitofusin2 in the regulation of mitochondrial dynamics

Abstract

Mitochondria in all cell types undergo frequent fission and fusion events, and these dynamics determine the overall morphology of the organelle in cells. Two important GTPases have been recently identified that regulate mitochondrial membrane activity, a dynamin related protein (DRP1) required for fission, and the novel fusion GTPase, Mitofusin2. Mitofusin2 is an outer mitochondrial membrane protein and, like other GTPases involved in membrane fusion events, the N-terminal GTPase domain is exposed to the cytosol, such that it could interact with and recruit potential cytosolic proteins. The work documented in this thesis aims towards understanding the specific role of this unique GTPase in regulating mitochondrial fusion events, and to identify potential interacting proteins that work together with Mfn2 to carry out this complex biochemical event. Two independent approaches were taken to identify interacting proteins, both a yeast two-hybrid screen and affinity chromatography using recombinant bacterial expressed Mfn2 protein as bait. (Abstract shortened by UMI.)