A Yeast Model of the Neurogenic Ataxia Retinitis Pigmentosa (NARP) T8993G Mutation in the Mitochondrial ATP Synthase-6 Gene
| Autor: | Jean-Paul di Rago, Stéphane Duvezin-Caubet, Joanna Rytka, Nahia Ezkurdia, Maïlis Bietenhader, Malgorzata Rak, Emmanuel Tetaud |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Mitochondrial disease Mutant Saccharomyces cerevisiae Mutation Missense Mitochondrion Models Biological Biochemistry Electron Transport Complex IV Adenosine Triphosphate Oxygen Consumption medicine Cytochrome c oxidase Molecular Biology biology ATP synthase Hydrolysis Wild type Cell Biology Mitochondrial Proton-Translocating ATPases biology.organism_classification medicine.disease Molecular biology Mitochondria Amino Acid Substitution Mitochondrial matrix biology.protein Ataxia Leigh Disease Protons Retinitis Pigmentosa |
| Zdroj: | Journal of Biological Chemistry. 282:34039-34047 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m703053200 |
| Popis: | NARP (neuropathy, ataxia, and retinitis pigmentosa) and MILS (maternally inherited Leigh syndrome) are mitochondrial disorders associated with point mutations of the mitochondrial DNA (mtDNA) in the gene encoding the Atp6p subunit of the ATP synthase. The most common and studied of these mutations is T8993G converting the highly conserved leucine 156 into arginine. We have introduced this mutation at the corresponding position (183) of yeast Saccharomyces cerevisiae mitochondrially encoded Atp6p. The "yeast NARP mutant" grew very slowly on respiratory substrates, possibly because mitochondrial ATP synthesis was only 10% of the wild type level. The mutated ATP synthase was found to be correctly assembled and present at nearly normal levels (80% of the wild type). Contrary to what has been reported for human NARP cells, the reverse functioning of the ATP synthase, i.e. ATP hydrolysis in the F(1) coupled to F(0)-mediated proton translocation out of the mitochondrial matrix, was significantly compromised in the yeast NARP mutant. Interestingly, the oxygen consumption rate in the yeast NARP mutant was decreased by about 80% compared with the wild type, due to a selective lowering in cytochrome c oxidase (complex IV) content. This finding suggests a possible regulatory mechanism between ATP synthase activity and complex IV expression in yeast mitochondria. The availability of a yeast NARP model could ease the search for rescuing mechanisms against this mitochondrial disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|