Mitochondria often exist as a dynamic tubular network. Individual mitochondria frequently divide or fuse with neighboring mitochondria in response to a variety of metabolic and cell division cues. Our laboratory is interested in the mechanism of mitochondrial division and how this mechanism is related to endocytosis. A first indication that these processes may be related came from our studies of dynamin-related protein (DRP-1) in the nematode C. elegans. We discovered that DRP-1 is important for the final stage of division of the mitochondrial outer membrane. This was surprising, because the protein sequence is very similar to that of dynamin, which we know mediates an early stage of clathrin mediated endocytosis. We hypothesize that division of the mitochondrial outer membrane is evolutionarily and mechanistically related to endocytic vesicle formation. The very first endosymbiontic bacterium would have retained parts of the endocytic machinery to divide the incipient mitochondrial membranes.

To confirm this hypothesis, we are looking for additional proteins that act both in endocytosis and in division of the mitochondrial outer membrane. We are focusing on two well-known players in endocytic vesicle formation, synaptojanin and endophilin, which might also be candidates for mitochondrial division. We tested the effect of the synaptojanin mutant unc-26(e205) on mitochondrial morphology using a GFP with a mitochondrial leader sequence under control of the myo-3 promoter. The mitochondria in C. elegans body wall muscles appear as a few large clumps rather than as numerous regularly shaped wild-type mitochondrial bodies. These clumps may arise from impaired mitochondrial division. Furthermore, this phenotype appears to be partially rescued by overexpression of DRP-1. Our data thus indicates that in C. elegans, synaptojanin itself plays a role in maintaining proper mitochondrial morphology. Currently, we are seeking to determine whether the morphology defect of unc-26(e205) mitochondria arises from impaired mitochondrial division or disruption of another mitochondrial process.