Regulation of mitochondrial trafficking by Myosin XIX during cell migration.
Myosin XIX (Myo19) is an actin-based molecular motor that is anchored to the outer mitochondria membrane (OMM) via its unique membrane binding motif. Myo19 is a strong effector of filopodia formation under cellular stress conditions mediated by glucose starvation, ROS and EGF. Filopodia are actin protrusions important for many cellular dynamic processes such as cell migration, angiogenesis, wound healing, limb regeneration and sensing extracellular environment, among others. In mammals, Myo19’s ability to induce filopodia is strongly coupled to mitochondrial transport on the actin filaments which is achieved by the enzymatic adaptation of its active motor as an ensemble of molecules bound to mitochondria. However, the cellular processes which are essentially required for triggering Myo19 based mitochondrial motility to filopodia are not known. In addition, the role of these mitochondria rich filopodia actin protrusions are yet to be coupled to their cellular functions. Cell migration being a fundamental process in both physiology and pathophysiology requires actin cytoskeleton remodeling, and hence we hypothesize that Myo19 will play a role during cell migration. Interestingly, we have found that siRNA mediated Myo19 knockdown cells exhibit a reduction in the rate of cell migration measured using 2D in-vitro cell scratch assay. This phenotype is most likely robust in several cell lines that we have explored. We have also begun to identify key signaling evens that may be related to triggering mitochondrial motility to filopodia. These findings provide the basis for the direct involvement of Myo19 in various physiological process that are manifested by actin protrusions.