Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia.

B H Robinson; J Ward; P Goodyer; A Baudet

doi:10.1172/JCI112453

Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia.

B H Robinson, J Ward, P Goodyer, and A Baudet

Published May 1, 1986 - More info

View PDF

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.