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

Abstract

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. 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. Although the mitochondrial network appeared morphologically unaltered, there was a significant defect of mitochondrial coupling associated with a reduction of the mitochondrial membrane potential. Our results suggest that the sharply reduced efficacy of oxidative phosphorylation in MFN2-related CMT2A may contribute to the pathophysiology of the axonal neuropathy.