Abstract
Defects of complex I of the mitochondrial respiratory chain are important causes of neurological disease. We report studies that demonstrate a severe deficiency of complex I activity with less severe abnormalities of complexes III and IV (less than 5, 63, and 30% of control values, respectively) in a skeletal muscle mitochondrial fraction from a 22-yr-old female with weakness, lactic acidemia, and the deposition of intramuscular neutral lipid. The observation that lipid accumulates in this and other patients with complex I deficiency suggests impaired mitochondrial fatty acid oxidation. To investigate this mechanism we have shown impaired flux through beta-oxidation [( U-14C]hexadecanoate oxidation was 66% of control rate) and accumulation of specific acyl-CoA ester intermediates. The changes in fatty acid metabolism in complex I deficiency are secondary to the reduced state within the mitochondrial matrix with low NAD+/NADH ratios.
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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Cytochrome-c Oxidase Deficiency
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Cytochromes / metabolism
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Electron Transport Complex II
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Electron Transport Complex III / metabolism
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Electron Transport Complex IV / metabolism
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Female
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Histocytochemistry
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Humans
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Kinetics
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Metabolism, Inborn Errors / metabolism*
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Metabolism, Inborn Errors / pathology
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Mitochondria, Muscle / metabolism*
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Multienzyme Complexes / metabolism
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Muscles / pathology
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NAD(P)H Dehydrogenase (Quinone)
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Neuromuscular Diseases / metabolism*
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Neuromuscular Diseases / pathology
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Oxidoreductases / metabolism
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Oxygen Consumption
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Quinone Reductases / deficiency*
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Quinone Reductases / metabolism
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Reference Values
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Succinate Dehydrogenase / metabolism
Substances
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Cytochromes
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Multienzyme Complexes
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Oxidoreductases
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Electron Transport Complex II
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Succinate Dehydrogenase
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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