Mgm1 Alters Membrane Topology and Promotes Local Membrane Bending to Drive Mitochondrial Membrane Fusion

Abstract

Cellular membrane remodeling events such as mitochondrial dynamics, vesicle budding and cell division rely on the large GTPases of the dynamin superfamily. Dynamins have long been characterized as fission molecules; however, how they mediate membrane fusion is largely unknown. Recently, we showed that the mitochondrial dynamin Mgm1 can mediate fusion by first tethering opposing membranes and undergoing nucleotide-dependent structural transition. However, it is still unclear how Mgm1 could act directly on the membrane to drive the fusion of tethered membranes. Here, we show that Mgm1 binding to the membrane could alter membrane topology and promote local membrane bending. By atomic force microscopy, we showed that Mgm1 created roughness and a tubulated structure on a supported lipid bilayer, and by monitoring giant liposomes Mgm1 recruited on and deformed the liposomes. These data suggest Mgm1 lipid interactions and changes in the protein/lipid complexes could apply forces onto the membrane to possibly promote fusion of opposing membrane. Together our data provide a possible mechanism of how Mgm1 mediates mitochondrial fusion and shed light onto how dynamins function as fusion molecules.