Immunological phenotyping of fibroblast cultures from patients with a mitochondrial respiratory chain deficit

Conventional approaches to the diagnosis of mitochondrial respiratory chain diseases, using enzyme assays and histochemistry, are laborious and give l imited information concerning the genetic basis of a deficiency. We have ev aluated the diagnostic value of 12 monoclonal antibodies to subunits of the four respiratory chain enzyme complexes and F1Fo-ATP synthase. Antibodies were used in immunological studies with skin fibroblast cultures derived fr om patients with diverse mitochondrial diseases, including patients in whic h the disease was caused by a nuclear genetic defect and patients known to harbor a heteroplasmic mutation in a mitochondrial tRNA gene. Immunoblottin g experiments permitted the identification of specific enzyme assembly defi cits and immunocytochemical studies provided clues regarding the genetic or igin of the disease. The immunological findings were in agreement with the biochemical and genetic data of the patients. Our study demonstrates that c haracterization of the fibroblast cultures with the monoclonal antibodies p rovides a convenient technique to complement biochemical assays and histoch emistry in the diagnosis of mitochondrial respiratory chain disorders.