Rodinova 2015 Abstract MiP2015

From Bioblast
Altered mitochondrial ultrastructure, reduced respiration and decreased level of PDH subunits in fibroblasts from 10 patients with Huntington’s disease.


Rodinova M, Kratochvílova H, Markova M, Spacilova J, Tesarova M, Klempir J, Liskova I, Elederova L, Juhasova J, Motlík J, Zeman J, Hansikova H (2015)

Event: MiP2015

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused due to expansion of the number of CAG repeats on the gene for huntingtin protein (htt). More than 36 CAG repeats lead to pathological extension of glutamine tract of htt which is connected with changes of secondary structure and malfunction of the htt. Mutant htt has been implicated in the disruption of multiple cellular processes, including mitochondrial functions whose impairment is emerging as a contributing factor to the pathogenesis of HD.

The aim of the study was to analyze the impact of HD on selected bioenergetics’ functions in cultivated skin fibroblasts of 10 patients with confirmed HD. All patients were heterozygotes in age between 31 and 74 years and the number of CAG triplet repeats on the mutated allele ranged between 40 and 58. All fibroblasts were obtained after informed consents. Fibroblasts obtained from 48 month old minipig boars transgenic for the N-terminal part of human mutated htt (TgHD) and WT controls were analyzed in parallel manner.

Mitochondrial ultrastructure, network and reactive oxygen species were visualized using fluorescent and transmission electron microscopy. Protein analysis of selected mitochondrial proteins was detected by immunoelectrophoretic methods. Functional disturbances were tested using high sensitive polarography.

Pathological changes in mitochondrial ultrastructure, like decreased number of cristae, swollen mitochondria or increased mitochondrial degradation were detected in all patient´s fibroblast lines in comparison to controls. Mitochondrial network was disintegrated and unequally distributed in patient´s cells. Ultrastructural changes of mitochondria and increased content of reactive oxygen species were found in TgHD minipig’s fibroblasts in comparison with WT. Protein analysis showed decreased level of pyruvate dehydrogenase complex (PDH) subunits E1-α, and mitochondrial complex I subunit NDUFA9 was detected in 9 patients out of 10.

Our results confirm mitochondrial disturbances in non-neuronal tissue like cultivated skin fibroblasts of HD patients and TgHD minipig model which are similar to phenotypes published in HD human neuronal cells or muscles.

O2k-Network Lab: CZ Prague Zeman J

Labels: MiParea: Respiration, mtDNA;mt-genetics, Patients  Pathology: Neurodegenerative  Stress:Mitochondrial disease  Organism: Human, Pig  Tissue;cell: Endothelial;epithelial;mesothelial cell, Fibroblast 

Enzyme: Complex I 

Event: A1, Oral  MiP2015 


1-Dept Pediatrics Adolescent Med; 2-Dept Neurology, First Fac Med, Charles Univ Prague and General Univ Hospital Prague, 3-Lab Cell Regeneration Cell Plasticity, Inst Animal Physiol Genetics, Libechov, Czech Republic. - [email protected]


Supported by: Czech-Norwegian Research Programme 7F14308, RVO-VFN64165

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