Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Poster Session I

4-POS Board 4 Unconventional Myosin 19 is a Novel Mitochondrial Membrane-anchored Molecular Motor and a Regulator of the Mitochondrial Network Boris Shneyer , Marko Usaj, Arnon Henn. Technion - Israel Institute of Technology, Haifa, Israel. Mitochondria undergoing continuous cycles of fission and fusion create a very dynamic network, which is essential for its proper functions. Mitochondria long-range motility relies on microtubule motors such as kinesin and dynein, however actin filaments and myosins have also been shown to interact and support mitochondria localization and dynamics. Recently, the actin- dependent motor Myosin 19 was found to localize to the mitochondria. However, the interaction of endogenous Myosin 19 with the mitochondria, the molecular details of this interaction, and its physiological role remain unknown. We initiated our investigation with bio-informatics analysis to have revealed a putative transmembrane (TM) region in the tail domain of Myosin 19, which is flanked with positive residues and predicted to form an amphiphilic α-helix. We demonstrate using subcellular fractionation, phase separation and carbonate extraction that endogenous Myosin 19 is anchored to the OMM revealing its amphiphilic nature. Furthermore, we show using proteinase K and carboxypeptidase Y digestion of purified mitochondria that Myosin 19 has an Ncyt-Ccyt topology. Remarkably, the predicted TM region is essential and sufficient to target Myosin 19 to the mitochondria. We show that Myosin 19 overexpression disrupts the mitochondrial network and causes it to be restricted to the perinuclear region. Interestingly, starvation causes Myosin 19 to re-localize to the tips of actin protrusions in the cell periphery. To this end, we present strong evidence that Myosin 19 is a monotopic membrane protein localized to mitochondria and may provide a linkage between the mitochondria and the actin cytoskeleton. The altered localization may reveal an additional role for Myosin 19 which is linked to mitochondria function and regulation. These results support the contribution of the actin cytoskeleton and myosin to mitochondrial dynamics.

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