A novel role for Myosin-Va in mitochondrial fission

Araujo, J. S.; Silva-Junior, R. M. P.; Zhang, T.; Schiavon, C. R.; Chu, Q.; Wu, M.; Pontes, C. L. S.; Souza, A. O.; Alberici, L. C.; Santos, A. M.; Ingle, S. B.; Saghatelian, A.; Spudich, J.; Manor, U.; Espreafico, E. M.

doi:10.1101/655803

bioRxiv · 10.1101/655803

A novel role for Myosin-Va in mitochondrial fission

Araujo, J. S.·Silva-Junior, R. M. P.·Zhang, T.·Schiavon, C. R.·Chu, Q.·Wu, M.·Pontes, C. L. S.·Souza, A. O.·Alberici, L. C.·Santos, A. M.·Ingle, S. B.·Saghatelian, A.·Spudich, J.·Manor, U.·Espreafico, E. M.

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Abstract

In cancer cells metabolic changes and mitochondrial morphology are coupled. It is known that the cytoskeleton and molecular motors are directly involved in regulating mitochondrial morphology. Here we show that myosin-Va, an actin-based molecular motor, is required for the malignant properties of melanoma cells and localizes to mitochondria in these cells. Knockdown of myosin-Va increases cellular respiration rates and ROS production and decreases glucose uptake and lactate secretion. In addition, knockdown of myosin-Va results in reduced mitochondrial fission and correspondingly elongated mitochondria. We show that myosin-Va interacts with the mitochondrial outer membrane protein Spire1C, an actin-regulatory protein implicated in mitochondrial fission, and that Spire1C recruits myosin-Va to mitochondria. Finally, we show that during mitochondrial fission myosin-Va localization to mitochondria increases, and that myosin-Va localizes to mitochondrial fission sites immediately adjacent to Drp1 punctae. We conclude that myosin-Va facilitates mitochondrial fission. These data implicate myosin-Va as a target for the Warburg effect in melanoma cells.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC=\"FIGDIR/small/655803v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (35K):\norg.highwire.dtl.DTLVardef@1130e72org.highwire.dtl.DTLVardef@196619org.highwire.dtl.DTLVardef@17e09edorg.highwire.dtl.DTLVardef@1bdc311_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Araujo, J. S., Silva-Junior, R. M. P., Zhang, T., Schiavon, C. R., Chu, Q., Wu, M., Pontes, C. L. S., Souza, A. O., Alberici, L. C., Santos, A. M., Ingle, S. B., Saghatelian, A., Spudich, J., Manor, U., Espreafico, E. M.. 2019-05-31. A novel role for Myosin-Va in mitochondrial fission. https://doi.org/10.1101/655803

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