Advertisement
Research Article Free access | 10.1172/JCI114409
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Watmough, N. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Bindoff, L. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Birch-Machin, M. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Jackson, S. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Bartlett, K. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Ragan, C. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Poulton, J. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Gardiner, R. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Sherratt, H. in: JCI | PubMed | Google Scholar
Department of Clinical Neuroscience, University of Newcastle upon Tyne, England.
Find articles by Turnbull, D. in: JCI | PubMed | Google Scholar
Published January 1, 1990 - More info
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.
Images.