title: Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission.
abstract: Several mitochondrial outer membrane proteins-mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (Mff), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51, respectively)-have been proposed to promote mitochondrial fission by recruiting the GTPase dynamin-related protein 1 (Drp1), but fundamental issues remain concerning their function. A recent study supported such a role for Mff but not for Fis1. In addition, it is unclear whether MiD49 and MiD51 activate or inhibit fission, because their overexpression causes extensive mitochondrial elongation. It is also unknown whether these proteins can act in the absence of one another to mediate fission. Using Fis1-null, Mff-null, and Fis1/Mff-null cells, we show that both Fis1 and Mff have roles in mitochondrial fission. Moreover, immunofluorescence analysis of Drp1 suggests that Fis1 and Mff are important for the number and size of Drp1 puncta on mitochondria. Finally, we find that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. These results demonstrate that multiple receptors can recruit Drp1 to mediate mitochondrial fission.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Losón
authors.forename: Zhiyin
authors.initials: Z
authors.lastname: Song
authors.forename: Hsiuchen
authors.initials: H
authors.lastname: Chen
authors.forename: David C
authors.initials: DC
authors.lastname: Chan
mesh_terms: D000818:Animals; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000235:genetics*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: C561064:FIS1 protein, mouse; C561316:MIEF1 protein, human; D008565:Membrane Proteins; C533267:Mff protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D010445:Peptide Elongation Factors; D034741:RNA, Small Interfering; C486391:Dnm1l protein, mouse; D034281:Dynamins