Abstract
Mutations in the human mtDNA gene encoding subunit III of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Poracoccus denitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g. lower H+/e ratio and lower deltapsi), but had similar CO activity. These results indicate that both substitutions (F263L > A212T) cause intrinsic uncoupling, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Ascorbic Acid / pharmacology
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DNA, Mitochondrial / genetics*
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Electron Transport Complex IV / genetics*
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Gene Deletion
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Gene Expression
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Humans
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Kinetics
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MELAS Syndrome / enzymology
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MELAS Syndrome / genetics*
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Onium Compounds / metabolism
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Optic Atrophies, Hereditary / enzymology
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Optic Atrophies, Hereditary / genetics*
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Organophosphorus Compounds / metabolism
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Paracoccus denitrificans / enzymology
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Paracoccus denitrificans / genetics
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Paracoccus denitrificans / growth & development
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Proton Pumps / metabolism
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Tetramethylphenylenediamine / pharmacology
Substances
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DNA, Mitochondrial
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Onium Compounds
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Organophosphorus Compounds
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Proton Pumps
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Electron Transport Complex IV
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Tetramethylphenylenediamine
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Ascorbic Acid
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tetraphenylphosphonium