Abstract
Large-scale deletions of mitochondrial DNA (mtDNA) are associated with a subgroup of mitochondrial encephalomyopathies. We studied seven patients with Kearns-Sayre syndrome or isolated ocular myopathy who harboured a sub-population of partially-deleted mitochondrial genomes in skeletal muscle. Variable cytochrome c oxidase (COX) deficiencies and reduction of mitochondrially-encoded polypeptides were found in affected muscle fibres, but while many COX-deficient fibres had increased levels of mutant mtDNA, they almost invariably had reduced levels of normal mtDNA. Our results suggest that a specific ratio between mutant and wild-type mitochondrial genomes is the most important determinant of a focal respiratory chain deficiency, even though absolute copy numbers may vary widely.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Blotting, Southern
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Cytochrome-c Oxidase Deficiency
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DNA Probes
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DNA, Mitochondrial / genetics*
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Electron Transport Complex IV / genetics
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Electron Transport Complex IV / metabolism
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Humans
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Immunohistochemistry
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In Situ Hybridization
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Kearns-Sayre Syndrome / enzymology
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Kearns-Sayre Syndrome / genetics*
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Kearns-Sayre Syndrome / pathology
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MELAS Syndrome / genetics
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MERRF Syndrome / genetics
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Mitochondrial Myopathies / enzymology
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Mitochondrial Myopathies / genetics*
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Mitochondrial Myopathies / pathology*
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Oculomotor Muscles / enzymology
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Oculomotor Muscles / pathology*
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Polymerase Chain Reaction / methods
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RNA / analysis
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RNA / genetics
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RNA, Mitochondrial
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Sequence Deletion*
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Succinate Dehydrogenase / genetics
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Succinate Dehydrogenase / metabolism
Substances
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DNA Probes
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DNA, Mitochondrial
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RNA, Mitochondrial
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RNA
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Succinate Dehydrogenase
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Electron Transport Complex IV