title: Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia.
abstract: The cultured skin fibroblasts from three patients with lacticacidemia were found to have low rates of 1-[14C]pyruvate oxidation in the face of normal pyruvate dehydrogenase activity. After incubation with 1 mM glucose, these three cell strains also exhibited lactate/pyruvate ratios which were three times greater than those of controls. In two of the patients, both ATP and oxygen consumption in fibroblast mitochondrial preparations was deficient with NAD-linked substrates but normal with succinate and ascorbate/N'N'N'N' tetramethyl phenylene diamine. In the third patient, ATP synthesis in mitochondrial preparations was deficient with all substrates tested. Measurement of Rotenone-sensitive NADH-cytochrome c reductase in mitochondrial preparations from skin fibroblasts showed that two of the patients had 14 and 18%, respectively, of control activity. In the third patient, cytochrome oxidase activity was 15% of that in controls. We conclude that respiratory chain defects can be demonstrated in cultured skin fibroblasts with consistency using a number of different techniques.
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone); D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D010101:Oxygen Consumption; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D011808:Quinone Reductases / Q000032:analysis; D012867:Skin / Q000378:metabolism*
chemical_list: D007773:Lactates; D011773:Pyruvates; D009243:NAD; D019344:Lactic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D003576:Electron Transport Complex IV