Mitochondrial Genome Maintenance 1 (Mgm1) Protein Alters Membrane Topology and Promotes Local Membrane Bending. Issue 16 (14th August 2015)

• Record Type: Journal Article
• Authors: Rujiviphat, Jarungjit; Wong, Michael K.; Won, Amy; Shih, Yu-ling; Yip, Christopher M.; McQuibban, G. Angus
• Is Part Of: Journal of molecular biology. Volume 427:Issue 16(2015:Aug. 15)
• Page Start: 2599
• Page End: 2609
• Publication Date: 2015-08-14
• Subjects: AFM atomic force microscopy -- CL cardiolipin -- DRP dynamin-related protein -- GED GTP effector domain -- IM inner membrane -- Mgm1 mitochondrial genome maintenance 1 -- PA phosphatidic acid -- PC phosphatidylcholine -- PS phosphatidylserine -- SLB supported lipid bilayer -- SUV small unilamellar vesicle; mitochondrial dynamics -- dynamin -- phospholipid -- membrane fusion -- fluorescence microscopy; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2015.03.006
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Large GTPases of the dynamin superfamily promote membrane fusion and division, processes that are crucial for intracellular trafficking and organellar dynamics. 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 previously 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. Graphical abstract: Highlights: Mgm1 is a membrane-remodeling dynamin that mediates mitochondrial membrane fusion. Mgm1 affects phospholipid movement and alters membrane topography. Mgm1 induces local membrane curvature. The membrane-remodeling activities of Mgm1 are enhanced in the presence of GTP. Membrane deformation explains Mgm1- and dynamin-mediated membrane fusion mechanism.