Mitochondrial Genome Maintenance 1 (Mgm1) Protein Alters Membrane Topology and Promotes Local Membrane Bending Jarungjit Rujiviphat 1 , Michael K. Wong 2 , Amy Won 2 , Yu-ling Shih 3 , Christopher M. Yip 1,2,4 and G. Angus McQuibban 1 1 - Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8 2 - Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada M5S 3G9 3 - Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan 4 - Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3E5 Correspondence to G. Angus McQuibban: 1 King's College Circle, Medical Sciences Building Room 5342, Toronto, Ontario, Canada M5S 1A8. angus.mcquibban@utoronto.ca http://dx.doi.org/10.1016/j.jmb.2015.03.006 Edited by B. Poolman Jarungjit Rujiviphat and G. Angus McQuibban Abstract Large GTPases of the dynamin superfamily promote membrane fusion and division, processes that are crucial for intracellular trafficking and organellar dy- namics. To promote membrane scission, dynamin proteins polymerize, wrap around, and constrict the membrane; however, the mechanism underlying their role in membrane fusion remains unclear. We previ- ously reported that the mitochondrial dynamin-related protein mitochondrial genome maintenance 1 (Mgm1) mediates fusion by first tethering opposing membranes and then undergoing a nucleotide-dependent structural transition. However, it is still unclear how Mgm1 directly affects the membrane to drive fusion of tethered membranes. Here, we show that Mgm1 association with the membrane alters the topography of the membrane, promoting local membrane bending. We also demonstrate that Mgm1 creates membrane ruffles resulting in the formation of tubular structures on both supported lipid bilayers and liposomes. These data suggest that Mgm1 membrane interactions impose a mechanical force on the membrane to overcome the hydrophilic repulsion of the phospholipid head groups and initiate the fusion reaction. The work reported here provides new insights into a possible mechanism of Mgm1-driven mitochondrial membrane fusion and sheds light into how members of the dynamin superfamily function as fusion molecules. © 2015 Elsevier Ltd. All rights reserved. Jarungjit Rujiviphat and G. Angus McQuibban Legend: The cover is representing a giant liposome being remodeled by Mgm1. 0022-2836/© 2015 Elsevier Ltd. All rights reserved. J Mol Biol (2015) xx, xxx–xxx Featured Arcle Please cite this article as: Rujiviphat Jarungjit, et al, Mitochondrial Genome Maintenance 1 (Mgm1) Protein Alters Membrane Topology and Promotes Local Membrane Bending, J Mol Biol (2015), http://dx.doi.org/10.1016/j.jmb.2015.03.006 IMF YJMBI-64713; No. of pages: 11; 4C: 1, 3, 4, 5, 6, 7, 8, 9