title: The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1.
abstract: Dynamin-related protein 1 (Drp1) is the GTP-hydrolyzing mechanoenzyme that catalyzes mitochondrial fission in the cell. Residing in the cytosol as dimers and tetramers, Drp1 is recruited by receptors on the mitochondrial outer membrane, where it further assembles into a helical ring that drives division via GTP-dependent constriction. The Drp1 receptor Mff is a major regulator of mitochondrial fission, and its overexpression results in increased fission. In contrast, the alternative Drp1 receptors MiD51 and MiD49 appear to recruit inactive forms of Drp1, because their overexpression inhibits fission. Using genetic and biochemical assays, we studied the interaction of Drp1 with Mff. We show that the insert B region of Drp1 inhibits Mff-Drp1 interactions, such that recombinant Drp1 mutants lacking insert B form a stable complex with Mff. Mff cannot bind to assembly-deficient mutants of Drp1, suggesting that Mff selectively interacts with higher-order complexes of Drp1. In contrast, the alternative Drp1 receptors MiD51 and MiD49 can recruit Drp1 dimers. Therefore Drp1 recruitment by Mff versus MiD51 and MiD49 may result in different outcomes because they recruit different subpopulations of Drp1 from the cytosol.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Raymond
authors.initials: R
authors.lastname: Liu
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 dchan@caltech.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Chan
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D034281:Dynamins / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010445:Peptide Elongation Factors / Q000235:genetics; D055503:Protein Multimerization
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010445:Peptide Elongation Factors; C000603499:mitochondrial fission factor, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins