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Adenine nucleotide translocase is involved in a mitochondrial coupling defect in MFN2-related Charcot–Marie–Tooth type 2A disease

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Abstract

Charcot–Marie–Tooth type 2A disease (CMT2A), a dominantly inherited peripheral neuropathy, is caused by mutations in MFN2, a mitochondrial fusion protein. Having previously demonstrated a mitochondrial coupling defect in CMT2A patients’ fibroblasts, we here investigate mitochondrial oxygen consumption and the expression of adenine nucleotide translocase (ANT) and uncoupling proteins from eight other patients with the disease. The mitochondrial uncoupling was associated with a higher respiratory rate, essentially involving complex II proteins. Furthermore, a twofold increase in the expression of ANT led to the reduced efficiency of oxidative phosphorylation in CMT2A cells, suggesting that MFN2 plays a role in controlling ATP/ADP exchanges.

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Abbreviations

CMT2A:

Charcot–Marie–Tooth type 2A disease

MFN2:

Mitofusin 2

ANT:

Adenine nucleotide translocase

OPA1:

Optic atrophy 1

cATR:

Carboxyatractyloside

UCP:

Uncoupling protein

MP:

Malate pyruvate

SR:

Succinate rotenone

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Acknowledgments

This work was supported by the Institut National de la Santé et de la Recherche Médicale, the University Hospital of Angers (PHRC 04-12), and the University of Angers, France. We are grateful to J. Hodbert, C. Wetterwald, and J. Alban for technical assistance and to K. Malkani for critical reading and comments on the manuscript.

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Authors and Affiliations

  1. INSERM, U694, Angers, 49000, France

    Virginie Guillet, Naïg Gueguen, Christophe Verny, Marc Ferre, Dominique Loiseau, Patrizia Amati-Bonneau, Dominique Bonneau, Pascal Reynier & Arnaud Chevrollier

  2. Département de Biochimie et Génétique, CHU d’Angers, Angers, 49000, France

    Naïg Gueguen, Marc Ferre, Chadi Homedan, Vincent Procaccio, Patrizia Amati-Bonneau, Dominique Bonneau, Pascal Reynier & Arnaud Chevrollier

  3. Faculté de Médecine, Université d’Angers, Angers, 49000, France

    Virginie Guillet, Christophe Verny, Marc Ferre, Dominique Loiseau, Vincent Procaccio, Dominique Bonneau & Pascal Reynier

  4. Département de Neurologie, CHU d’Angers, Angers, 49000, France

    Christophe Verny

  5. CNRS UMR6214, INSERM U771, 49000, Angers, France

    Vincent Procaccio

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  1. Virginie Guillet
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Corresponding author

Correspondence to Arnaud Chevrollier.

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Guillet, V., Gueguen, N., Verny, C. et al. Adenine nucleotide translocase is involved in a mitochondrial coupling defect in MFN2-related Charcot–Marie–Tooth type 2A disease. Neurogenetics 11, 127–133 (2010). https://doi.org/10.1007/s10048-009-0207-z

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  • DOI: https://doi.org/10.1007/s10048-009-0207-z

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