Increase in oxidative key enzymes in a case of muscle ubiquinol-cytochrome c reductase deficiency

Abstract

In a 29-year-old patient suffering from exertional muscle intolerance with a ubiquinol-cytochrome c reductase deficiency related to a cytochrome b gene point mutation of the mitochondrial DNA, we conducted a study of the aims of which were: (1) to test whether changes in the maximum activities of muscle key enzymes of the main energy-producing pathways occur, (2) to address the issue of whether fibers of different types are equally affected in their enzymatic machinery involved in energy production, and (3) to correlate the results obtained with histochemical and 31P NMR spectroscopy data. When compared to results obtained in six normal subjects, our study clearly shows that the type I fibers of the patient virtually all contained subsarcolemmal mitochondrial aggregates and increased activities of succinate dehydrogenase and cytochrome c oxidase; microdissected type I fibers also displayed a significant increase in both citrate synthase and beta-hydroxyacyl-CoA dehydrogenase, two key enzymes of mitochondrial oxidative metabolism. Despite these changes in the patient's muscle, its whole energy-producing machinery remained impaired as revealed by a slowed post-exercise recovery of phosphocreatine.