title: A role for septin 2 in Drp1-mediated mitochondrial fission.
abstract: Mitochondria are essential eukaryotic organelles often forming intricate networks. The overall network morphology is determined by mitochondrial fusion and fission. Among the multiple mechanisms that appear to regulate mitochondrial fission, the ER and actin have recently been shown to play an important role by mediating mitochondrial constriction and promoting the action of a key fission factor, the dynamin-like protein Drp1. Here, we report that the cytoskeletal component septin 2 is involved in Drp1-dependent mitochondrial fission in mammalian cells. Septin 2 localizes to a subset of mitochondrial constrictions and directly binds Drp1, as shown by immunoprecipitation of the endogenous proteins and by pulldown assays with recombinant proteins. Depletion of septin 2 reduces Drp1 recruitment to mitochondria and results in hyperfused mitochondria and delayed FCCP-induced fission. Strikingly, septin depletion also affects mitochondrial morphology in Caenorhabditis elegans, strongly suggesting that the role of septins in mitochondrial dynamics is evolutionarily conserved.
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France U604 Inserm, Paris, France USC2020 INRA, Paris, France.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pagliuso
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France U604 Inserm, Paris, France USC2020 INRA, Paris, France.
authors.forename: To Nam
authors.initials: TN
authors.lastname: Tham
authors.affiliation: Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Stevens
authors.affiliation: Unité d'Analyse d'Images Biologiques Institut Pasteur, Paris, France CNRS UMR 3691, Paris, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Lagache
authors.affiliation: Bioaxial, Paris, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Persson
authors.affiliation: Imagopole, Citech Institut Pasteur, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Salles
authors.affiliation: Unité d'Analyse d'Images Biologiques Institut Pasteur, Paris, France CNRS UMR 3691, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Olivo-Marin
authors.affiliation: Bioaxial, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oddos
authors.affiliation: Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Spang
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France U604 Inserm, Paris, France USC2020 INRA, Paris, France fabrizia.stavru@pasteur.fr pcossart@pasteur.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France U604 Inserm, Paris, France USC2020 INRA, Paris, France fabrizia.stavru@pasteur.fr pcossart@pasteur.fr.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Stavru
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D005075:Biological Evolution; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D058112:Septins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D000205:Actomyosin; D020558:GTP Phosphohydrolases; C000602252:SEPTIN2 protein, human; D058112:Septins; C110768:DNM1L protein, human; D034281:Dynamins
keywords: Drp1; mitochondrial dynamics; septin