title: Mitochondrial coupling defect in Charcot-Marie-Tooth type 2A disease.
abstract: OBJECTIVE
  Mutations of the mitofusin 2 gene (MFN2) may account for at least a third of the cases of Charcot-Marie-Tooth disease type 2 (CMT2). This study investigates mitochondrial cellular bioenergetics in MFN2-related CMT2A.
  
  
  METHODS
  Mitochondrial network morphology and metabolism were studied in cultures of skin fibroblasts obtained from four CMT2A patients harboring novel missense mutations of the MFN2 gene.
  
  
  RESULTS
  Although the mitochondrial network appeared morphologically unaltered, there was a significant defect of mitochondrial coupling associated with a reduction of the mitochondrial membrane potential.
  
  
  CONCLUSIONS
  Our results suggest that the sharply reduced efficacy of oxidative phosphorylation in MFN2-related CMT2A may contribute to the pathophysiology of the axonal neuropathy.
authors: Institut National de la Santé et de la Recherche Médicale U694, Angers, France.
authors: Dominique
authors: D
authors: Loiseau
authors: Arnaud
authors: A
authors: Chevrollier
authors: Christophe
authors: C
authors: Verny
authors: Virginie
authors: V
authors: Guillet
authors: Naïg
authors: N
authors: Gueguen
authors: Marie-Anne
authors: MA
authors: Pou de Crescenzo
authors: Marc
authors: M
authors: Ferré
authors: Marie-Claire
authors: MC
authors: Malinge
authors: Agnès
authors: A
authors: Guichet
authors: Guillaume
authors: G
authors: Nicolas
authors: Patrizia
authors: P
authors: Amati-Bonneau
authors: Yves
authors: Y
authors: Malthièry
authors: Dominique
authors: D
authors: Bonneau
authors: Pascal
authors: P
authors: Reynier
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D017209:Apoptosis; D002478:Cells, Cultured; D002607:Charcot-Marie-Tooth Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D020558:GTP Phosphohydrolases; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000235:genetics; D020125:Mutation, Missense; D017382:Reactive Oxygen Species; D012867:Skin / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human