UNIGE document Scientific Article
previous document  unige:20858  next document
add to browser collection
Title

Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli

Authors
Hudec, Roman
Lopreiato, Raffaele
Ermak, Gennady
Lim, Dmitri
Malorni, Walter
Davies, Kelvin J. A.
show hidden authors show all authors [1 - 10]
Published in EMBO Molecular Medicine. 2010, vol. 2, no. 12, p. 490-503
Abstract Huntington's disease (HD), a genetic neurodegenerative disease caused by a polyglutamine expansion in the Huntingtin (Htt) protein, is accompanied by multiple mitochondrial alterations. Here, we show that mitochondrial fragmentation and cristae alterations characterize cellular models of HD and participate in their increased susceptibility to apoptosis. In HD cells, the increased basal activity of the phosphatase calcineurin dephosphorylates the pro-fission dynamin related protein 1 (Drp1), increasing its mitochondrial translocation and activation, and ultimately leading to fragmentation of the organelle. The fragmented HD mitochondria are characterized by cristae alterations that are aggravated by apoptotic stimulation. A genetic analysis indicates that correction of mitochondrial elongation is not sufficient to rescue the increased cytochrome c release and cell death observed in HD cells. Conversely, the increased apoptosis can be corrected by manoeuvres that prevent fission and cristae remodelling. In conclusion, the cristae remodelling of the fragmented HD mitochondria contributes to their hypersensitivity to apoptosis.
Keywords Animals*ApoptosisCell LineCells, CulturedCytochromes c/metabolismFemaleGTP Phosphohydrolases/genetics/metabolismHumansHuntington Disease/genetics/metabolism/*physiopathologyMaleMiceMicroscopy, Electron, TransmissionMicrotubule-Associated Proteins/genetics/metabolismMitochondria/genetics/*physiology/ultrastructureMitochondrial Proteins/genetics/metabolismModels, BiologicalNeurons/cytology/metabolismProtein Transport
Identifiers
PMID: 21069748
Full text
Structures
Research group Les mitochondries dans la vie cellulaire (850)
Citation
(ISO format)
COSTA, Veronica et al. Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli. In: EMBO Molecular Medicine, 2010, vol. 2, n° 12, p. 490-503. https://archive-ouverte.unige.ch/unige:20858

188 hits

0 download

Update

Deposited on : 2012-05-23

Export document
Format :
Citation style :