title: Inactivation of Pif1 helicase causes a mitochondrial myopathy in mice.
abstract: Mutations in genes coding for mitochondrial helicases such as TWINKLE and DNA2 are involved in mitochondrial myopathies with mtDNA instability in both human and mouse. We show that inactivation of Pif1, a third member of the mitochondrial helicase family, causes a similar phenotype in mouse. pif1-/- animals develop a mitochondrial myopathy with respiratory chain deficiency. Pif1 inactivation is responsible for a deficiency to repair oxidative stress-induced mtDNA damage in mouse embryonic fibroblasts that is improved by complementation with mitochondrial isoform mPif1(67). These results open new perspectives for the exploration of patients with mtDNA instability disorders.
authors.affiliation: IRCAN, CNRS UMR 7284/INSERM U1081/UNS, Faculté de Médecine, Nice, France; Service de Génétique Médicale, Hôpital Archet 2, CHU de Nice, Nice, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bannwarth
authors.affiliation: IRCAN, CNRS UMR 7284/INSERM U1081/UNS, Faculté de Médecine, Nice, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Berg-Alonso
authors.affiliation: IRCAN, CNRS UMR 7284/INSERM U1081/UNS, Faculté de Médecine, Nice, France; Service de Génétique Médicale, Hôpital Archet 2, CHU de Nice, Nice, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Augé
authors.affiliation: IRCAN, CNRS UMR 7284/INSERM U1081/UNS, Faculté de Médecine, Nice, France; Service de Génétique Médicale, Hôpital Archet 2, CHU de Nice, Nice, France.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Fragaki
authors.affiliation: Department of Medicine, Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Jill E
authors.initials: JE
authors.lastname: Kolesar
authors.affiliation: IRCAN, CNRS UMR 7284/INSERM U1081/UNS, Faculté de Médecine, Nice, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Lespinasse
authors.affiliation: Centre Commun de Microscopie Electronique Appliquée, Faculté des Sciences, Université de Nice Sophia Antipolis, Nice, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lacas-Gervais
authors.affiliation: Service de Neuropathologie, Hôpital Pasteur, CHU de Nice, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Burel-Vandenbos
authors.affiliation: INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), équipe "contrôle métabolique des morts cellulaires", Nice Sophia-Antipolis University, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Villa
authors.affiliation: Department of Medicine, Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Belmonte
authors.affiliation: Service de Neuropathologie, Hôpital Pasteur, CHU de Nice, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.affiliation: INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), équipe "contrôle métabolique des morts cellulaires", Nice Sophia-Antipolis University, France.
authors.forename: Jean-Ehrland
authors.initials: JE
authors.lastname: Ricci
authors.affiliation: INSERM U955, E10, Université Paris-Est, Créteil, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Gherardi
authors.affiliation: Université de Montréal, Institut de Recherche en Immunologie et en Cancérologie, 2950 chemin de Polytechnique, Montréal, Québec H3T 1J4, Canada.
authors.forename: Lea
authors.initials: L
authors.lastname: Harrington
authors.affiliation: Department of Medicine, Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Kaufman
authors.affiliation: IRCAN, CNRS UMR 7284/INSERM U1081/UNS, Faculté de Médecine, Nice, France; Service de Génétique Médicale, Hôpital Archet 2, CHU de Nice, Nice, France. Electronic address: paquis@hermes.unice.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004265:DNA Helicases / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000502:physiology; D020868:Gene Silencing; D051379:Mice; D018345:Mice, Knockout; D028361:Mitochondrial Diseases; D017240:Mitochondrial Myopathies / Q000235:genetics*
chemical_list: D004265:DNA Helicases; C517519:Pif1 protein, mouse
keywords: Mitochondrial disease; Mitochondrial myopathy; Pif1 helicase; mtDNA instability