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

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 elongat

SUBMITTER: Costa V 

PROVIDER: S-EPMC3044888 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature