title: Dnm1 forms spirals that are structurally tailored to fit mitochondria.
abstract: Dynamin-related proteins (DRPs) are large self-assembling GTPases whose common function is to regulate membrane dynamics in a variety of cellular processes. Dnm1, which is a yeast DRP (Drp1/Dlp1 in humans), is required for mitochondrial division, but its mechanism is unknown. We provide evidence that Dnm1 likely functions through self-assembly to drive the membrane constriction event that is associated with mitochondrial division. Two regulatory features of Dnm1 self-assembly were also identified. Dnm1 self-assembly proceeded through a rate-limiting nucleation step, and nucleotide hydrolysis by assembled Dnm1 structures was highly cooperative with respect to GTP. Dnm1 formed extended spirals, which possessed diameters greater than those of dynamin-1 spirals but whose sizes, remarkably, were equal to those of mitochondrial constriction sites in vivo. These data suggest that Dnm1 has evolved to form structures that fit the dimensions of mitochondria.
authors.affiliation: Department of Molecular and Cellular Biology, Center for Genetics and Development, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Ingerman
authors.forename: Edward M
authors.initials: EM
authors.lastname: Perkins
authors.forename: Michael
authors.initials: M
authors.lastname: Marino
authors.forename: Jason A
authors.initials: JA
authors.lastname: Mears
authors.forename: J Michael
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Hinshaw
authors.forename: Jodi
authors.initials: J
authors.lastname: Nunnari
mesh_terms: D019281:Dimerization; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009994:Osmolar Concentration; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae