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Treatment of CoQ(10) Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects

Lopez, LC; Quinzii, CM; Area, E; Naini, A; Rahman, S; Schuelke, M; Salviati, L; ... Hirano, M; + view all (2010) Treatment of CoQ(10) Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects. PLOS ONE , 5 (7) , Article e11897. 10.1371/journal.pone.0011897. Green open access

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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.Methodology/Principal Findings: 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 mu M 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/Significance: 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.

Type: Article
Title: Treatment of CoQ(10) Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0011897
Publisher version: http://dx.doi.org/10.1371/journal.pone.0011897
Language: English
Additional information: © 2010 López et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by U.S. National Institutes of Health (NIH) grants HD32062 and NS11766, by grants from the Muscular Dystrophy Association (MDA), and by the Marriott Mitochondrial Disorders Clinical Research Fund (MMDCRF). LCL was supported by a post-doctoral fellowship from the Ministerio de Educación y Ciencia, Spain. CMQ is supported by the MDA. LS is supported by Telethon grant GGP09207. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: COENZYME Q(10) DEFICIENCY, DIPHOSPHATE SYNTHASE SUBUNIT-2, RESPIRATORY-CHAIN DYSFUNCTION, MITOCHONDRIAL COMPLEX I, FRIEDREICH ATAXIA, CEREBELLAR-ATAXIA, OXIDATIVE STRESS, MUTATIONS, MUTANTS, NEPHROPATHY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/121556
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