Annals of Neurology · 2006 · 70 citations · 16 references
Life SciencesCell BiologyNeurobiologyBioenergeticsMitochondrial BiologyNeurodegenerationHuntington DiseaseMitochondrial BiochemistryMitochondrial BioenergeticsMitochondrial Calcium HomeostasisMitochondrial DysfunctionMitochondrial PhysiologyCalcium Transport Across MitochondriaCalcium-dependent Mitochondrial MetabolismElectron Transport Chain DysfunctionMitochondrial Calcium HandlingMitochondrial NeuropathologyMuscle AtrophyNeurodegenerative Mitochondrial DysfunctionRespiratory Chain Dysfunction
OBJECTIVE: The aim of the present work was the detection of Mitochondrial dysfunction of Huntington's disease (HD). METHODS: We investigated muscle and muscle mitochondria of 14- to 16-week-old R6/2 mice in comparison with wild-type mice. RESULTS: Atrophic fibers, increased fuchsinophilic aggregates, and reduced cytochrome c oxidase (15%) were found in HD muscle. With swelling measurements and Ca2+ accumulation experiments, a decreased stability of HD mitochondria against Ca2+-induced permeability transition was detected. Complex I-dependent respiration of HD mitochondria was more sensitive to inhibition by adding 10 microm Ca2+ than wild-type mitochondria. INTERPRETATION: Data suggest that the decreased stability of HD mitochondria against Ca2+ contributes to energetic depression and cell atrophy.
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