1. A role for septin 2 in Drp1‐mediated mitochondrial fission
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Anne Spang, To Nam Tham, Julia Stevens, Alessandro Pagliuso, Thibault Lagache, Pascale Cossart, Roger Persson, Jean-Christophe Olivo-Marin, Stephane Oddos, Audrey Salles, Fabrizia Stavru, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biozentrum, Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Bioaxial, Imagopole (CITECH), Institut Pasteur [Paris], We gratefully acknowledge the kind financial support of the Institut Pasteur (Paris), the France-BioImaging infrastructure network supported by the French National Research Agency (ANR-10–INSB–04, Investments for the future), and the Région Ile-de-France (program DIM-Malinf). TL is funded by a Bourse Roux fellowship from Institut Pasteur and the Labex IBEID. FS is a CNRS senior research fellow, and PC is a Senior International HHMI Scholar. Work in the EMBO reports Vol 17 |No 6 | 2016 ª 2016 The Authors EMBOreports Septin 2 in mitochondrial fission Alessandro Pagliuso et al 870 Published online: May 23, 2016 Spang Laboratory is funded by the University of Basel and Swiss National Science Foundation (CRSII 3_141956). The Cossart Laboratory is supported by Institut Pasteur, Inserm (U604), ANR (Grant 12-BSV3-0017-03Mitopatho), and ERC (Grant 670823BacCellEpi)., ANR-12-BSV3-0017,MITOPATHO,Rôle des mitochondries durant l'invasion des cellules par les bactéries Listeria et Shigella(2012), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Cossart, Pascale, Stavru, Fabrizia, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Analyse d'images biologiques - BioImage Analysis (AIQ), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], ANR: Mitopatho,12-BSV3-0017-03, vicente, marie-therese, BLANC - Rôle des mitochondries durant l'invasion des cellules par les bactéries Listeria et Shigella - - MITOPATHO2012 - ANR-12-BSV3-0017 - BLANC - VALID, and Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID
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0301 basic medicine ,[SDV]Life Sciences [q-bio] ,MESH: Actomyosin ,Mitochondrion ,Septin ,Biochemistry ,GTP Phosphohydrolases ,News & Views ,MESH: Gene Silencing ,Membrane & Intracellular Transport ,Cytoskeleton ,Caenorhabditis elegans ,biology ,MESH: Mitochondrial Proteins ,Articles ,Actomyosin ,MESH: Caenorhabditis elegans Proteins ,Biological Evolution ,Mitochondria ,Cell biology ,[SDV] Life Sciences [q-bio] ,mitochondrial fusion ,Gene Knockdown Techniques ,Mitochondrial fission ,biological phenomena, cell phenomena, and immunity ,Microtubule-Associated Proteins ,Dynamins ,MESH: Septins ,endocrine system ,MESH: GTP Phosphohydrolases ,Immunoprecipitation ,MESH: Mitochondria ,MESH: Biological Evolution ,macromolecular substances ,Drp1 ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Article ,Mitochondrial Proteins ,03 medical and health sciences ,mitochondrial dynamics ,septin ,Genetics ,Humans ,Gene Silencing ,Caenorhabditis elegans Proteins ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Molecular Biology ,MESH: Humans ,030102 biochemistry & molecular biology ,biology.organism_classification ,MESH: Gene Knockdown Techniques ,MESH: Mitochondrial Dynamics ,MESH: Microtubule-Associated Proteins ,030104 developmental biology ,MESH: HeLa Cells ,DNAJA3 ,Septins ,HeLa Cells - Abstract
International audience; 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.
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