The impact of mitochondrial tRNA mutations on the amount of ATP synthase differs in the brain compared to other tissues
| Autor: | Hana Hansikova, Tomas Honzik, Lukas Stiburek, Marketa Tesarova, Laszlo Wenchich, Evzenie Tietzeova, Olga Brantova, Daniela Fornuskova, Jiri Zeman |
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| Přispěvatelé: | First Faculty of Medicine, Charles University [Prague] (CU) |
| Rok vydání: | 2008 |
| Předmět: |
Male
Muscle Fibers Skeletal Respiratory chain Mitochondrion MELAS syndrome Oxidative Phosphorylation Fatal Outcome 0302 clinical medicine Electrophoresis Gel Two-Dimensional Child ComputingMilieux_MISCELLANEOUS 0303 health sciences COX — cytochrome c oxidase ATP synthase biology MERRF syndrome Life Sciences Brain Mitochondrial Proton-Translocating ATPases Mitochondria Biochemistry Organ Specificity RNA Transfer Lys Molecular Medicine Female Adolescent Immunoblotting Oxidative phosphorylation Electron Transport 03 medical and health sciences Oxygen Consumption medicine Humans Cytochrome c oxidase Muscle Skeletal Molecular Biology 030304 developmental biology Point mutation Infant Newborn medicine.disease Leigh syndrome Molecular biology Tissue specificity Kinetics Protein Subunits Mutation biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Basis of Disease Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2008, 1782 (5), pp.317. ⟨10.1016/j.bbadis.2008.02.001⟩ |
| ISSN: | 0925-4439 |
| Popis: | The impact of point mutations in mitochondrial tRNA genes on the amount and stability of respiratory chain complexes and ATP synthase (OXPHOS) has been broadly characterized in cultured skin fibroblasts, skeletal muscle samples, and mitochondrial cybrids. However, less is known about how these mutations affect other tissues, especially the brain. We have compared OXPHOS protein deficiency patterns in skeletal muscle mitochondria of patients with Leigh (8363G>A), MERRF (8344A>G), and MELAS (3243A>G) syndromes. Both mutations that affect mt-tRNALys (8363G>A, 8344A>G) resulted in severe combined deficiency of complexes I and IV, compared to an isolated severe defect of complex I in the 3243A>G sample (mt-tRNALeu(UUR)). Furthermore, we compared obtained patterns with those found in the heart, frontal cortex, and liver of 8363G>A and 3243A>G patients. In the frontal cortex mitochondria of both patients, the patterns of OXPHOS deficiencies differed substantially from those observed in other tissues, and this difference was particularly striking for ATP synthase. Surprisingly, in the frontal cortex of the 3243A>G patient, whose ATP synthase level was below the detection limit, the assembly of complex IV, as inferred from 2D-PAGE immunoblotting, appeared to be hindered by some factor other than the availability of mtDNA-encoded subunits. |
| Databáze: | OpenAIRE |
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