title: M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.
abstract: Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.
authors.affiliation: CNRS UMR5237, Centre de Recherche en Biochimie Macromoléculaire, Montpellier, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Cambier
authors.forename: Patrice
authors.initials: P
authors.lastname: Rassam
authors.forename: Béatrice
authors.initials: B
authors.lastname: Chabi
authors.forename: Karima
authors.initials: K
authors.lastname: Mezghenna
authors.forename: René
authors.initials: R
authors.lastname: Gross
authors.forename: Eric
authors.initials: E
authors.lastname: Eveno
authors.forename: Charles
authors.initials: C
authors.lastname: Auffray
authors.forename: Chantal
authors.initials: C
authors.lastname: Wrutniak-Cabello
authors.forename: Anne-Dominique
authors.initials: AD
authors.lastname: Lajoix
authors.forename: Pascal
authors.initials: P
authors.lastname: Pomiès
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D004579:Electron Transport; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D038081:Organogenesis; D010101:Oxygen Consumption; D021382:Protein Sorting Signals; D021381:Protein Transport
chemical_list: D000255:Adenosine Triphosphate; D015415:Biomarkers; D007328:Insulin; D024101:Mitochondrial Proteins; D021382:Protein Sorting Signals; C546538:UQCC2 protein, human; C546537:M19 protein, mouse