Coenzyme Q10 depletion is comparatively less detrimental to human cultured skin fibroblasts than respiratory chain complex deficiencies.
The oxidative stress possibly resulting from an inherited respiratory chain (RC) deficiency was investigated in a series of human cultured skin fibroblasts presenting either ubiquinone depletion or isolated defect of the various RC complexes. Taken as an index for superoxide overproduction, a significant induction of superoxide dismutase activity was observed in complex V-deficient fibroblasts harboring the NARP-mutation in the ATPase 6 gene. Superoxide dismutase induction was also noticed, albeit to a lesser extent, in complex II-deficient fibroblasts with a mutation in the nuclear gene encoding the flavoprotein subunit of the succinate dehydrogenase. No sign of oxidative stress could be found in ubiquinone-depleted fibroblasts. In all cases but complex IV-defect, increased oxidative stress was associated with increased cell death. In glucose-rich medium, apoptosis appeared as the main cell death process associated with all types of RC defect. However, similar to the great variations in oxidative stress associated with the various types of RC defect, we found that apoptotic features differed noticeably between defects. No indication of increased cell death was found in ubiquinone-depleted fibroblasts.
Geromel
Vanna
V
Unité de Recherches sur les Handicaps Génétiques de I'Enfant (INSERM U393) Hôpital Necker-Enfants-Malades, Paris, France.
Rötig
Agnès
A
Munnich
Arnold
A
Rustin
Pierre
P
D000154:Aconitate Hydratase / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003067:Coenzymes; D019610:Cytoprotection; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000378:metabolism*; D018384:Oxidative Stress; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency*
D017304:Annexin A5; D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; D007521:Isocitrate Dehydrogenase; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000154:Aconitate Hydratase; C024989:coenzyme Q10