Mitochondrial coupling defect in Charcot–Marie–Tooth type 2A disease

Authors

  • Dominique Loiseau PharmD,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Université Angers Départements de, Centre Hospitalier Universitaire Angers, Angers, France
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    • D.L. and A.C. contributed equally to this work.

  • Arnaud Chevrollier PhD,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
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    • D.L. and A.C. contributed equally to this work.

  • Christophe Verny MD,

    1. Neurologie et, Centre Hospitalier Universitaire Angers, Angers, France
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  • Virginie Guillet BS,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
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  • Naïg Gueguen PhD,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
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  • Marie-Anne Pou De Crescenzo PhD,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Université Angers Départements de, Centre Hospitalier Universitaire Angers, Angers, France
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  • Marc Ferré Eng,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
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  • Marie-Claire Malinge PharmD,

    1. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
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  • Agnès Guichet MD,

    1. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
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  • Guillaume Nicolas MD, PhD,

    1. Neurologie et, Centre Hospitalier Universitaire Angers, Angers, France
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  • Patrizia Amati-Bonneau MD,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
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  • Yves Malthièry MD, PhD,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Université Angers Départements de, Centre Hospitalier Universitaire Angers, Angers, France
    3. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
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  • Dominique Bonneau MD, PhD,

    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Université Angers Départements de, Centre Hospitalier Universitaire Angers, Angers, France
    3. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
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  • Pascal Reynier MD, PhD

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale U694, France
    2. Université Angers Départements de, Centre Hospitalier Universitaire Angers, Angers, France
    3. Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
    • INSERM U694, Département de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, F-49033 France
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Abstract

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

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