D.L. and A.C. contributed equally to this work.
Mitochondrial coupling defect in Charcot–Marie–Tooth type 2A disease
Version of Record online: 19 APR 2007
Copyright © 2007 American Neurological Association
Annals of Neurology
Volume 61, Issue 4, pages 315–323, April 2007
How to Cite
Loiseau, D., Chevrollier, A., Verny, C., Guillet, V., Gueguen, N., Pou De Crescenzo, M.-A., Ferré, M., Malinge, M.-C., Guichet, A., Nicolas, G., Amati-Bonneau, P., Malthièry, Y., Bonneau, D. and Reynier, P. (2007), Mitochondrial coupling defect in Charcot–Marie–Tooth type 2A disease. Ann Neurol., 61: 315–323. doi: 10.1002/ana.21086
- Issue online: 24 APR 2007
- Version of Record online: 19 APR 2007
- Manuscript Accepted: 22 DEC 2007
- Manuscript Revised: 17 NOV 2007
- Manuscript Received: 5 JUL 2007
- Institut National de la Santé et de la Recherche Médicale
- University Hospital of Angers (PHRC 04-12)
- University of Angers, France, and Retina France
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. Ann Neurol 2007;61:315–323