Kratochvilova 2015 Abstract MiP2015

From Bioblast
Mitochondrial dysfunction in Niemann Pick type C1 patientΒ΄s cells and tissues.


Kratochvilova H, Rodinova M, Hulkova H, Knopova S, Dvorakova L, Novakova M, Hansikova H, Zeman J, Tesarova M (2015)

Event: MiP2015

The cholesterol levels in mitochondria are approximately 40-fold lower than in the plasma membrane and 4.5-fold lower than in the endoplasmic reticulum (ER). Therefore mitochondria are sensitive to changes in absolute cholesterol content. Mitochondria require cholesterol for biogenesis and membrane maintenance as well as steroid biosynthesis.

Niemann-Pick type C1 disease is an autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in NPC1 gene. Mutation in NPC1 leads to endosomal cholesterol accumulation and defects in cellular cholesterol homeostasis. Mitochondrial cholesterol increase was observed in Niemann-Pick type C1-deficient cells, which affects some mitochondrial function.

The aim of our project was to study impact of altered distribution of cellular cholesterol due to NPC1 mutation on oxidative phosphorylation complexes and mitochondrial ultrastructure in available cells (fibroblasts) and tissues (brain, liver) from two NPC1 patients.

Filipin test confirmed impaired cholesterol distribution in cultivated NPC1 fibroblast. Moreover altered mitochondrial network and ultrastructure was observed in fibroblast cell lines compared to the control. In brain mitochondria, pronounced deficiency in native amount of complex V and complex III was found in both patient samples. While reduced level of ATP synthase was observed in liver mitochondria only in P2. However levels of complex I, III and IV were increased in all analyzed liver samples. Enzymatic activities of respiratory chain complexes were decreased in liver as well as in brain NPC1 mitochondria.

Impaired cholesterol distribution in NPC1 tissues and cells influences steady state levels and function of all OXPHOS complexes.

β€’ O2k-Network Lab: CZ Prague Zeman J

Labels: MiParea: Respiration, nDNA;cell genetics, Patients  Pathology: Neurodegenerative  Stress:Mitochondrial disease  Organism: Human  Tissue;cell: Nervous system, Liver, Fibroblast 

Enzyme: Complex I, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase 

Event: A1, Poster  MiP2015 


1-Dept Pediatrics Adolescent Med, 2-Inst Inherited Metabolic Disorders, First Fac Med, Charles Univ Prague and General Univ Hospital Prague, Czech Republic. - [email protected]


The study was supported by research project RVO-VFN64165, IGA NT 13114-4, UNCE 204011 and GAUK 1308214.

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