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 1-1[4Cjpyruvate 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

The Use of Skin Fibroblast Cultures in the Detection of Respiratory Chain Defects in Patients with Lacticacidemia

“…* NAD H cytochrome reductase (roteno ne sensitive) was measured in fibroblast mitochondria as described previously (3). LIP ratio in fibroblasts after incubation with glucose was determined as in Mat erials and Meth ods.…”

“…This is easil y demonstrated in the most severel y affected patients with the fatal infantile form of the disea se. Patients with severe defects in either complex I or cytochrome oxidase had complexe s that were only partially The inb orn errors of metabolism kn own to be primary causes of lacticacidemia include defects in pyru vate carboxylase ( I), th e pyru vate dehydrogenase complex (2), and the respiratory chain (3). Altho ugh the first two produce devastating result s in early life in th ose affected, the majorit y of report ed cases with respiratory chain defects have thus far been older children or adults (4,5).…”

The N Terminus of the Qcr7 Protein of the Cytochromebc 1 Complex Is Not Essential for Import into Mitochondria in Saccharomyces cerevisiae but Is Essential for Assembly of the Complex

“…The mixture was incubated at 37°C for 45 min, and the reaction was stopped with 80 mM perchloric acid. Proteins were pelleted, and the supernatant was assayed for the amount of ATP synthesized by using a hexokinase/glucose-6-phosphate dehydrogenase coupled assay (18), and the NADPH generated was measured by an Eppendorf fluorimeter.…”

Heteroplasmy in Chronic External Ophthalmoplegia: Clinical and Molecular Observations

“…Conversely, dysfunction of a given site along the electro n transport chain has been associated with man y seemingly disparate clinical phenotypes (40,41): some cases of norm oglycemic congenital lactic acidosis (42)(43)(44)(45); individual cases with Leigh's polioencephalopathy (46)(47)(48); MELAS syndrome (49-51); MERRF syndrome (26,(52)(53)(54)(55); and proximal myopath y with easy fatiguability (2). Despite their biochemical and histologic similarities, they have been described as distinct clinical syndromes.…”