Mitochondrial Myopathy with a Defect of Mitochondrial-Protein Transport

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Abstract
The clinical and biochemical heterogeneity of the mitochondrial myopathies is now well established.1 , 2 Recent work has focused on identifying the molecular basis of these disorders and has demonstrated specific deficiencies of nuclear-encoded polypeptides in some patients3 , 4 and deletions of mitochondrial DNA in others.5 , 6 Deficiencies of nuclear-encoded polypeptides may be due to reduced synthesis, increased degradation, or defective transport of protein precursors from cell cytosol to mitochondria. We describe a patient with a pure myopathy and evidence of a deficiency of respiratory-chain Complexes I to IV. Immunoblotting of muscle mitochondrial preparations showed specific deficiencies of both the iron-sulfur protein of Complex III ("Rieske" protein) and the 27.2-kd subunit of succinate dehydrogenase. Similar experiments with muscle homogenates indicated a deficiency of the 27.2-kd subunit of succinate dehydrogenase and normal levels of the precursor Rieske protein. These results suggest that the cause of the myopathy is a defect in the transport of the Rieske protein into mitochondria in addition to the succinate dehydrogenase deficiency.