title: Treatment of CoQ(10) deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects.
abstract: BACKGROUND
  Coenzyme Q(10) (CoQ(10)) and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.
  
  
  RESULTS
  To test these concepts, we have evaluated the effects of CoQ(10), coenzyme Q(2) (CoQ(2)), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10) deficiency. A final concentration of 5 microM of each compound was chosen to approximate the plasma concentration of CoQ(10) of patients treated with oral ubiquinone. CoQ(10) supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10) deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.
  
  
  CONCLUSIONS
  THESE RESULTS INDICATE THAT: 1) pharmacokinetics of CoQ(10) in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ(10) in the mitochondrial respiratory chain under conditions of CoQ(10) deficiency; and 3) oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10) deficiencies should be treated with CoQ(10) supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2). Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Luis C
authors.initials: LC
authors.lastname: López
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
authors.forename: Estela
authors.initials: E
authors.lastname: Area
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimauro
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D013481:Superoxides / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*
chemical_list: D013481:Superoxides; D014451:Ubiquinone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C024989:coenzyme Q10; C036619:idebenone; D001205:Ascorbic Acid