title: Membrane tethering and nucleotide-dependent conformational changes drive mitochondrial genome maintenance (Mgm1) protein-mediated 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. Here we have characterized by cryo-electron microscopy and in vitro liposome fusion assays how the mitochondrial dynamin Mgm1 may mediate membrane fusion. Using cryo-EM, we first demonstrate that the Mgm1 complex is able to tether opposing membranes to a gap of ∼15 nm, the size of mitochondrial cristae folds. We further show that the Mgm1 oligomer undergoes a dramatic GTP-dependent conformational change suggesting that s-Mgm1 interactions could overcome repelling forces at fusion sites and that ultrastructural changes could promote the fusion of opposing membranes. Together our findings provide mechanistic details of the two known in vivo functions of Mgm1, membrane fusion and cristae maintenance, and more generally shed light onto how dynamins may function as fusion proteins.
authors.affiliation: Department of Biotechnology and Food Engineering Technion, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Abutbul-Ionita
authors.forename: Jarungjit
authors.initials: J
authors.lastname: Rujiviphat
authors.forename: Iftach
authors.initials: I
authors.lastname: Nir
authors.forename: G Angus
authors.initials: GA
authors.lastname: McQuibban
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
mesh_terms: D003461:Crystallography; D005583:Fourier Analysis; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008561:Membrane Fusion; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D008081:Liposomes; C082883:MGM1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D010718:Phosphatidylserines; D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins