CMT 4A and 2K: Mitochondrial complex I deficiency in GDAP1-related autosomal dom

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Neurogenetics. 2008 Dec 17.

Mitochondrial complex I deficiency in GDAP1-related autosomal

dominant Charcot-Marie-Tooth disease (CMT2K).

Cassereau J, Chevrollier A, Gueguen N, Malinge MC, Letournel F,

Nicolas G, L, Ferre M, Verny C, Dubas F, Procaccio V, Amati-

Bonneau P, Bonneau D, Reynier P.

INSERM, U694, 4 rue Larrey, Angers, 49933, France.

Mutations in GDAP1, an outer mitochondrial membrane protein

responsible for recessive Charcot-Marie-Tooth disease (CMT4A), have

also been associated with CMT2K, a dominant form of the disease. The

three CMT2K patients we studied carried a novel dominant GDAP1

mutation, C240Y (c.719G > A). Mitochondrial respiratory chain complex

I activity in fibroblasts from CMT2K patients was 40% lower than in

controls, whereas the tubular mitochondria were 33% larger in

diameter and the mitochondrial mass was 20% greater. Thus, besides

the regulatory role GDAP1 plays in mitochondrial network dynamics, it

may also be involved in energy production and in the control of

mitochondrial volume.