title: Human cultured skin fibroblasts survive profound inherited ubiquinone depletion.
abstract: Beside its role in electron transfer in the mitochondrial respiratory chain, ubiquinone is known to prevent lipid peroxidation and DNA damage by trapping cellular free radicals. Thanks to its antioxidant properties, ubiquinone may represent an important factor controlling both necrotic and apoptotic processes. We have investigated the consequences of a profound inherited ubiquinone depletion on cultured skin fibroblasts of a patient presenting with encephalomyopathy. Interestingly, cell respiration, mitochondrial oxidation of various substrates, and cell growth of ubiquinone-deficient fibroblasts were only partially decreased. Moreover, these cells did not apparently overproduce superoxide anions or lipoperoxides. Finally, apoptosis did not increase as compared to control, even after serum deprivation. These observations suggest that ubiquinone may not play a major role in the antioxidant defenses of cultured fibroblasts and that its role in controlling oxidative stress and apoptosis may greatly vary across cell types, especially as not all tissues were equally affected in the patient despite the widespread ubiquinone depletion in vivo.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant (INSERM U393) Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75743 Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Geromel
authors.forename: N
authors.initials: N
authors.lastname: Kadhom
authors.forename: I
authors.initials: I
authors.lastname: Ceballos-Picot
authors.forename: D
authors.initials: D
authors.lastname: Chrétien
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: P
authors.initials: P
authors.lastname: Rustin
mesh_terms: D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D003067:Coenzymes; D019610:Cytoprotection / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D008564:Membrane Potentials; D017237:Mitochondrial Encephalomyopathies / Q000188:drug therapy / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000502:physiology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D003067:Coenzymes; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D006861:Hydrogen Peroxide; D007501:Iron; C024989:coenzyme Q10