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Mitochondrial coupling defect in Charcot–Marie–Tooth type 2A disease
Author(s) -
Loiseau Dominique,
Chevrollier Arnaud,
Verny Christophe,
Guillet Virginie,
Gueguen Naïg,
Pou De Crescenzo MarieAnne,
Ferré Marc,
Malinge MarieClaire,
Guichet Agnès,
Nicolas Guillaume,
AmatiBonneau Patrizia,
Malthièry Yves,
Bonneau Dominique,
Reynier Pascal
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21086
Subject(s) - mfn2 , mitochondrion , missense mutation , biology , oxidative phosphorylation , bioenergetics , gene , microbiology and biotechnology , mitochondrial fusion , mitochondrial dna , genetics , mutation , cancer research , biochemistry
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. Interpretation Our results suggest that the sharply reduced efficacy of oxidative phosphorylation in MFN2 ‐related CMT2A may contribute to the pathophysiology of the axonal neuropathy. Ann Neurol 2007;61:315–323