| There are three dynamin related proteins (DRPs) control mitochondrial fusion and division. DRPs function via GTP driven self-assembly to modify membranes, and are traditionally involved in membrane scission events. Thus, our understanding of how they mediate membrane fusion events has remained elusive. An added complication to mitochondrial fusion is the intricately organized nature of the inner mitochondrial membrane (IMM). This dissertation gives insight into the mechanism of IMM fusion, a process that is carried out by the DRP Mgm1. In addition of providing evidence the Mgm1 does in fact work to fuse the IMM, we also found that it has a role in the maintenance of cristae during fusion events. Interestingly, Mgm1 exists as two isoforms: a membrane tethered long isoform (l-Mgm1) and a peripheral membrane short isoform (s-Mgm1). Analysis of these isoforms illustrates a model for where l-Mgm1 acts as a membrane anchor while s-Mgm1 is the powerhouse that requires GTPase activity. Further analysis of Mgm1 indicates that its affinity for the IMM specific phospholipid, cardiolipin, is important not only for its membrane fusion and cristae maintenance roles, but for overall mitochondrial function as well. |
