MITOCHONDRIAL MYOPATHY WITH SUCCINATE-DEHYDROGENASE AND ACONITASE DEFICIENCY - ABNORMALITIES OF SEVERAL IRON-SULFUR PROTEINS

Recently, we described a patient with severe exercise intolerance and episodic myoglobinuria, associated with marked impairment of succinate oxidation and deficient activity of succinate dehydrogenase and aconi tase in muscle mitochondria (I ). We now report additional enzymatic a nd immunological characterization of mitochondria. In addition to seve re deficiency of complex II, manifested by reduction of succinate dehy drogenase and succinate:coenzyme Q oxidoreductase activities to 12 and 22% of normal, respectively, complex III activity was reduced to 37% and rhodanese to 48% of normal. Furthermore, although complex I activi ty was not measured, immunoblot analysis of complex I showed deficienc y of the 39-,24-,13-, and 9-kD peptides with lesser reductions of the 51- and 18-kD peptides. Immunoblots of complex III showed markedly red uced levels of the mature Rieske protein in mitochondria and elevated levels of its precursor in the cytosol, suggesting deficient uptake in to mitochondria. Immunoreactive aconitase was also low. These data, to gether with the previous documentation of low amounts of the 30-kD iro n-sulfur protein and the 13.5-kD subunit of complex II, compared to ne ar normal levels of the 70-kD protein suggest a more generalized abnor mality of the synthesis, import, processing, or assembly of a group of proteins containing iron-sulfur clusters.