title: Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission.
abstract: Mitochondrial fission is important for organelle transport, inheritance, and turnover, and alterations in fission are seen in neurological disease. In mammals, mitochondrial fission is executed by dynamin-related protein 1 (Drp1), a cytosolic guanosine triphosphatase that polymerizes and constricts the organelle. Recruitment of Drp1 to mitochondria involves receptors including Mff, MiD49, and MiD51. MiD49/51 form foci at mitochondrial constriction sites and coassemble with Drp1 to drive fission. Here, we solved the crystal structure of the cytosolic domain of human MiD51, which adopts a nucleotidyltransferase fold. Although MiD51 lacks catalytic residues for transferase activity, it specifically binds guanosine diphosphate and adenosine diphosphate. MiD51 mutants unable to bind nucleotides were still able to recruit Drp1. Disruption of an additional region in MiD51 that is not part of the nucleotidyltransferase fold blocked Drp1 recruitment and assembly of MiD51 into foci. MiD51 foci are also dependent on the presence of Drp1, and after scission they are distributed to daughter organelles, supporting the involvement of MiD51 in the fission apparatus.
authors: Department of Biochemistry and 2 Australian Research Council Centre of Excellence in Coherent X-Ray Science, La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3086, Australia.
authors: Viviane
authors: V
authors: Richter
authors: Catherine S
authors: CS
authors: Palmer
authors: Laura D
authors: LD
authors: Osellame
authors: Abeer P
authors: AP
authors: Singh
authors: Kirstin
authors: K
authors: Elgass
authors: David A
authors: DA
authors: Stroud
authors: Hiromi
authors: H
authors: Sesaki
authors: Marc
authors: M
authors: Kvansakul
authors: Michael T
authors: MT
authors: Ryan
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003460:Crystallization; D018360:Crystallography, X-Ray; D034281:Dynamins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006153:Guanosine Diphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C561316:MIEF1 protein, human; D024101:Mitochondrial Proteins; D010445:Peptide Elongation Factors; D006153:Guanosine Diphosphate; D000244:Adenosine Diphosphate; C486391:Dnm1l protein, mouse; D034281:Dynamins