Mitochondrial complex I deficiency in GDAP1-related autosomal dominant Charcot-Marie-Tooth disease (CMT2K).
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.
Cassereau
Julien
J
INSERM, U694, 4 rue Larrey, Angers, 49933, France.
Chevrollier
Arnaud
A
Gueguen
Naïg
N
Malinge
Marie-Claire
MC
Letournel
Franck
F
Nicolas
Guillaume
G
Richard
Laurence
L
Ferre
Marc
M
Verny
Christophe
C
Dubas
Frédéric
F
Procaccio
Vincent
V
Amati-Bonneau
Patrizia
P
Bonneau
Dominique
D
Reynier
Pascal
P
D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010375:Pedigree
C118663:GDAP protein; D009419:Nerve Tissue Proteins; D042967:Electron Transport Complex I