title: Expression of respiratory chain deficiencies in human cultured cells.
abstract: The expression of respiratory chain deficiencies was studied in cultured skin fibroblasts and B lymphoblastoid cell lines from patients with mitochondrial disorders. The genotype and phenotype of the cells were found to be dramatically different depending on the cell type and metabolic environment. In all cases, respiratory chain deficiencies gradually disappeared during the cell proliferation. However, in the presence of uridine, deficiencies were maintained in cultured skin fibroblasts. Accordingly, in cells harbouring a population of deleted mtDNA, the addition of uridine in the culture medium maintained the proportion of deleted mtDNA. In Epstein-Barr virus transformed lymphocytes, while a normal respiratory chain activity could be measured, deleted mtDNA was still present in high proportions (> 60% of the total mtDNA). The persistence of the deleted mtDNA was observed under all metabolic conditions tested, even when energy production from glycolysis was restricted. Finally, prenatal diagnosis of such a respiratory chain deficiency (cytochrome c oxidase deficiency) was performed in three cases. In all of them, a normal cytochrome c oxidase activity was measured in the cultured amniocytes. The children were born and are presenting no sign of an eventual affection.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U12, Hôpital des Enfants-Malades, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Bourgeron
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: P
authors.initials: P
authors.lastname: Amati
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: P
authors.initials: P
authors.lastname: Rustin
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D030401:Cytochrome-c Oxidase Deficiency; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012016:Reference Values; D012867:Skin / Q000378:metabolism*; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D013384:Succinate Cytochrome c Oxidoreductase; D003576:Electron Transport Complex IV; D014529:Uridine