Abstract
Mitochondria are dynamic organelles that continually divide and fuse with one another. These processes facilitate the control of mitochondrial morphology and respond to cell metabolic demands, such as ATP production, Ca2+ homeostasis and cell apoptosis. The excessive mitochondrial division is associated with neuronal cell death and neuronal dysfunction. Moreover, abnormal mitochondrial morphology can be found in many neurological disorders. Drp1 (dynamin-related protein 1) is a critical protein that facilitates mitochondrial division. However, the regulatory mechanism remains largely unclear. Cdk5 (cyclin dependent kinase 5) is implicated in neuronal death and survival. Previously, we found that Drp1 phosphorylated by Cdk5 in vitro. The goal of this thesis is to characterize the effects of Cdk5 dependent post-translational modification on Drp1 function. Overexpression of Drp1 S616D phospho-mimetic mutant led mitochondrial dynamic balance toward fusion and promoted Drp1 translocation to mitochondria. Our results suggest that Cdk5 phosphorylation of Drp1 at Ser-616 affects Drp1 protein function and mediates translocation of Drp1 to mitochondria. We consider Cdk5 phosphorylation is one of the mitochondrial division regulatory machineries.