Abstract |
This study aimed to understand the pathogenesis of a new mtDNA-related etiology of Leigh syndrome. We identified the T9176G mutation as the molecular basis of Leigh syndrome in a child and looked for alterations in cellular ATP production. We then modeled the new mtDNA mutation in E. coli and analyzed ATP synthesis, hydrolysis, and the ability of the mutated enzyme to pump protons. Our results suggest that the T9176G change results in a novel, fully assembled enzyme which inhibits the holoenzyme probably by blocking the proton pathway.
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Authors | R Carrozzo, J Murray, O Capuano, A Tessa, G Chichierchia, M R Neglia, R A Capaldi, F M Santorelli |
Journal | Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
(Neurol Sci)
Vol. 21
Issue 5 Suppl
Pg. S983-4
( 2000)
ISSN: 1590-1874 [Print] Italy |
PMID | 11382202
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Mitochondrial
- Adenosine Triphosphate
- Adenosine Triphosphatases
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Topics |
- Adenosine Triphosphatases
(genetics, metabolism)
- Adenosine Triphosphate
(biosynthesis, genetics)
- Brain
(enzymology, pathology, physiopathology)
- Child
- Child, Preschool
- DNA Mutational Analysis
- DNA, Mitochondrial
(genetics)
- Electron Transport
(genetics)
- Escherichia coli
(genetics)
- Female
- Genes
(genetics)
- Humans
- Leigh Disease
(enzymology, genetics, physiopathology)
- Models, Genetic
- Point Mutation
(genetics)
- Protein Structure, Tertiary
(genetics)
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