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.
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.
Authors: Frank N Gellerich; Zemfira Gizatullina; Huu P Nguyen; Sonata Trumbeckaite; Stefan Vielhaber; Enn Seppet; Stephan Zierz; Bernhard Landwehrmeyer; Olaf Riess; Stephan von Hörsten; Frank Striggow Journal: J Biol Chem Date: 2008-07-07 Impact factor: 5.157