title: Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation.
abstract: 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.
authors.affiliation: Neurogenetics Unit, IRCCS Neuromed, Pozzilli, IS, Italy. neurogen@neuromed.it
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
authors.forename: Milena
authors.initials: M
authors.lastname: Cannella
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sgarbi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Maglione
authors.forename: Alessandra
authors.initials: A
authors.lastname: Falleni
authors.forename: Paola
authors.initials: P
authors.lastname: Lenzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baracca
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cislaghi
authors.forename: Carsten
authors.initials: C
authors.lastname: Saft
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ragona
authors.forename: Matteo A
authors.initials: MA
authors.lastname: Russo
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Thompson
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Solaini
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
mesh_terms: 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