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Metab Brain Dis. 2018 Dec;33(6):2005-2017. doi: 10.1007/s11011-018-0308-1. Epub 2018 Aug 17.

Mitochondrial alterations accompanied by oxidative stress conditions in skin fibroblasts of Huntington's disease patients.

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Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland.
Department of Medical Biology and Genetics, University of Gdańsk, Gdańsk, Poland.
Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland.
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093, Warsaw, Poland.


Huntington disease (HD) is an autosomal dominant neurodegenerative disorder manifesting as progressive impairment of motor function and different neuropsychiatric symptoms caused by an expansion of CAG repeats in huntingtin gene (HTT). Mitochondrial dysfunction and bioenergetic defects can contribute to the course of the disease, however, the molecular mechanism underlying this process is still largely unknown. In this study, we aimed to determine several mitochondrial parameters in HD fibroblasts and assess their relevance to the disease progression as well as to value mitochondrial pathology in peripheral cells as disease potential biomarker. We showed that HD fibroblasts demonstrate significantly lower growth rate compared to control fibroblasts despite the lack of cell cycle perturbations. In order to investigate mitochondrial contribution to cell growth differences between HD and healthy cells, we provided insight into various mitochondrial parameters. Conducted experiments have revealed a significant reduction of the ATP level in HD fibroblasts accompanied by a decrease in mitochondrial metabolic activity in relation to the cells from healthy donors. Importantly, there were no differences in the mitochondrial membrane potential (mtΔΨ) and OXPHOS complexes' levels. Slightly increased level of mitochondrial superoxide (mt. O2•-), but not cytosolic reactive oxygen species (cyt. ROS), has been demonstrated. We have also observed significantly elevated levels of some antioxidant enzymes (SOD2 and GR) which may serve as an indicator of antioxidant defense system in HD patients. Thus, we suggest that mitochondrial alterations in skin fibroblasts of Huntington's disease patients might be helpful in searching for novel disease biomarkers.


Fibroblasts; Huntington disease; Mitochondria; Oxidative stress

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