Mitochondrial coupling defect in CMT 2A

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Ann Neurol. 2007 Apr 19;61(4):315-323

Mitochondrial coupling defect in Charcot-Marie-Tooth type 2A disease.

Loiseau D, Chevrollier A, Verny C, Guillet V, Gueguen N, Pou De

Crescenzo MA, Ferre M, Malinge MC, Guichet A, Nicolas G, Amati-

Bonneau P, Malthiery Y, Bonneau D, Reynier P.

Institut National de la Sante et de la Recherche Medicale U694,

France.

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.