Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects

• Published in: PloS one 2010-07, Vol.5 (7), p.e11897
• Main Authors: López, Luis C., Quinzii, Catarina M., Area, Estela, Naini, Ali, Rahman, Shamima, Schuelke, Markus, Salviati, Leonardo, DiMauro, Salvatore, Hirano, Michio
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; Alzheimer's disease; Analogs; Antioxidants; Apoptosis; Ascorbic acid; ATP; Bioavailability; Bioenergetics; Biosynthesis; Cell death; Cellular manufacture; Chains; Clinical trials; Coenzyme Q10; Defects; Dietary supplements; Electron transport; Fibroblasts; Genetics and Genomics/Disease Models; Genetics and Genomics/Genetics of Disease; Lipophilic; Mitochondria; Mutation; Neurological Disorders; Neurological Disorders/Neurogenetics; Neurological Disorders/Neuromuscular Diseases; Neurology; Normalizing; Oxidative phosphorylation; Oxidative stress; Patients; Pharmacokinetics; Pharmacology; Phosphorylation; Ratios; Respiration; Rodents; Skin; Superoxide; Ubiquinone; Vitamin C
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0011897

Background Coenzyme Q10 (CoQ10) 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. Methodology/Principal Findings To test these concepts, we have evaluated the effects of CoQ10, coenzyme Q2 (CoQ2), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ10 deficiency. A final concentration of 5 µM of each compound was chosen to approximate the plasma concentration of CoQ10 of patients treated with oral ubiquinone. CoQ10 supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ10 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/Significance These results indicate that: 1) pharmacokinetics of CoQ10 in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ10 in the mitochondrial respiratory chain under conditions of CoQ10 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 CoQ10 deficiencies should be treated with CoQ10 supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ2. Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present.