title: Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission.
abstract: Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.
authors.affiliation: Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Mears
authors.forename: Laura L
authors.initials: LL
authors.lastname: Lackner
authors.forename: Shunming
authors.initials: S
authors.lastname: Fang
authors.forename: Elena
authors.initials: E
authors.lastname: Ingerman
authors.forename: Jodi
authors.initials: J
authors.lastname: Nunnari
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Hinshaw
mesh_terms: D020285:Cryoelectron Microscopy; D034281:Dynamins / Q000737:chemistry; D020558:GTP Phosphohydrolases / Q000737:chemistry*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry*; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae; D034281:Dynamins