Mitochondrial coupling defect in Charcot-Marie-Tooth type 2A disease.
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.
Loiseau
Dominique
D
Institut National de la Santé et de la Recherche Médicale U694, Angers, France.
Chevrollier
Arnaud
A
Verny
Christophe
C
Guillet
Virginie
V
Gueguen
Naïg
N
Pou de Crescenzo
Marie-Anne
MA
Ferré
Marc
M
Malinge
Marie-Claire
MC
Guichet
Agnès
A
Nicolas
Guillaume
G
Amati-Bonneau
Patrizia
P
Malthièry
Yves
Y
Bonneau
Dominique
D
Reynier
Pascal
P
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
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human