Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation.
Mutated huntingtin is expressed in nervous and non nervous system included lymphoblasts. Eneregetic metabolism is impaired in Huntington's disease (HD) and other neurodegenerative diseases. Human HD lymphoblasts have provided clear-cut data on mitochondnal disruption. Here we report morphological, morphometric and membrane potential differences in mitochondria from lymphoblasts obtained from patients homozygous and heterozygous for the CAG mutation, and controls. Homozygotes, who despite a similar age at onset show a more aggressive phenotype than heterozygotes, had giant mitochondria and a reduced membrane potential. We argue that early mitochondrial impairment at basal level may affect the severity of HD progression in patients.
Squitieri
Ferdinando
F
Neurogenetics Unit, IRCCS Neuromed, Pozzilli, IS, Italy. neurogen@neuromed.it
Cannella
Milena
M
Sgarbi
Gianluca
G
Maglione
Vittorio
V
Falleni
Alessandra
A
Lenzi
Paola
P
Baracca
Alessandra
A
Cislaghi
Giuliana
G
Saft
Carsten
C
Ragona
Giuseppe
G
Russo
Matteo A
MA
Thompson
Leslie M
LM
Solaini
Giancarlo
G
Fornai
Francesco
F
D002461:Cell Line, Transformed; D004734:Energy Metabolism / Q000235:genetics; D006720:Homozygote; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000378:metabolism / Q000648:ultrastructure*; D008564:Membrane Potentials; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D009154:Mutation; D010641:Phenotype