Abstract
The functional consequences of large heteroplasmic mtDNA deletions were investigated in a group of 6 patients with chronic progressive external ophthalmoplegia (CPEO) syndromes. State III respiration rates corrected for age were low with site I and II substrates in all cases and cytochrome oxidase activity was depressed. The severity of impairment varied and is consistent with inclusion of a variable percentage of non-functioning mitochondria (with deleted mtDNA) in the pellet. Western blot studies with a holocomplex antibody battery revealed no abnormalities in subunit content of complexes III and IV. A deficiency of several complex I subunits in 3 cases suggests that abnormal nuclear-mitochondrial regulation of complex I assembly may follow large mtDNA deletions.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Chromosome Deletion
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Cytochrome-c Oxidase Deficiency*
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DNA, Mitochondrial / genetics*
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Electron Transport
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Electron Transport Complex III / deficiency*
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Electron Transport Complex III / genetics
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Electron Transport Complex IV / genetics
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Female
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Glutamates / metabolism
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Glutamic Acid
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Humans
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Male
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Middle Aged
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Mitochondria / metabolism
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NAD(P)H Dehydrogenase (Quinone)
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Ophthalmoplegia / genetics
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Ophthalmoplegia / metabolism*
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Oxidative Phosphorylation
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Oxygen Consumption
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Pyruvates / metabolism
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Pyruvic Acid
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Quinone Reductases / deficiency*
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Quinone Reductases / genetics
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RNA, Transfer / genetics
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Succinates / metabolism
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Succinic Acid
Substances
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DNA, Mitochondrial
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Glutamates
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Pyruvates
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Succinates
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Glutamic Acid
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Pyruvic Acid
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RNA, Transfer
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Succinic Acid
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NAD(P)H Dehydrogenase (Quinone)
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Quinone Reductases
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Electron Transport Complex IV
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Electron Transport Complex III