CMT 2A: Adenine nucleotide translocase is involved in a mitochondrial coupling d

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Neurogenetics. 2009 Jul 18.

Adenine nucleotide translocase is involved in a mitochondrial coupling defect in

MFN2-related Charcot-Marie-Tooth type 2A disease.

Guillet V, Gueguen N, Verny C, Ferre M, Homedan C, Loiseau D, Procaccio V,

Amati-Bonneau P, Bonneau D, Reynier P, Chevrollier A.

INSERM, U694, Angers, 49000, France.

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.