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Effect of Coenzyme Q10 supplementation on mitochondrial electron transport chain activity and mitochondrial oxidative stress in Coenzyme Q10 deficient human neuronal cells.
Int J Biochem Cell Biol. 2014 May; 50:60-3.IJ

Abstract

Primary Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with a heterogeneous clinical presentation. Common presenting features include both muscle and neurological dysfunction. Muscle abnormalities can improve, both clinically and biochemically following CoQ10 supplementation, however neurological symptoms are only partially ameliorated. At present, the reasons for the refractory nature of the neurological dysfunction remain unknown. In order to investigate this at the biochemical level we evaluated the effect of CoQ10 treatment upon a previously established neuronal cell model of CoQ10 deficiency. This model was established by treatment of human SH-SY5Y neuronal cells with 1 mM para-aminobenzoic acid (PABA) which induced a 54% decrease in cellular CoQ10 status. CoQ10 treatment (2.5 μM) for 5 days significantly (p<0.0005) decreased the level of mitochondrial superoxide in the CoQ10 deficient neurons. In addition, CoQ10 treatment (5 μM) restored mitochondrial membrane potential to 90% of the control level. However, CoQ10 treatment (10 μM) was only partially effective at restoring mitochondrial electron transport chain (ETC) enzyme activities. ETC complexes II/III activity was significantly (p<0.05) increased to 82.5% of control levels. ETC complexes I and IV activities were restored to 71.1% and 77.7%, respectively of control levels. In conclusion, the results of this study have indicated that although mitochondrial oxidative stress can be attenuated in CoQ10 deficient neurons following CoQ10 supplementation, ETC enzyme activities appear partially refractory to treatment. Accordingly, treatment with >10 μM CoQ10 may be required to restore ETC enzyme activities to control level. Accordingly, these results have important implication for the treatment of the neurological presentations of CoQ10 deficiency and indicate that high doses of CoQ10 may be required to elicit therapeutic efficacy.

Authors+Show Affiliations

Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.Neurometabolic Unit, National Hospital, London, UK; Department of Clinical Pathology and Metabolic Unit, Great Ormond Street Hospital for Children, London, UK.Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.Neurometabolic Unit, National Hospital, London, UK.Neurometabolic Unit, National Hospital, London, UK.Metabolic Unit, Great Ormond Street Hospital for Children, London, UK.Neurometabolic Unit, National Hospital, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. Electronic address: iain.hargreaves@uclh.nhs.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24534273

Citation

Duberley, K E., et al. "Effect of Coenzyme Q10 Supplementation On Mitochondrial Electron Transport Chain Activity and Mitochondrial Oxidative Stress in Coenzyme Q10 Deficient Human Neuronal Cells." The International Journal of Biochemistry & Cell Biology, vol. 50, 2014, pp. 60-3.
Duberley KE, Heales SJ, Abramov AY, et al. Effect of Coenzyme Q10 supplementation on mitochondrial electron transport chain activity and mitochondrial oxidative stress in Coenzyme Q10 deficient human neuronal cells. Int J Biochem Cell Biol. 2014;50:60-3.
Duberley, K. E., Heales, S. J., Abramov, A. Y., Chalasani, A., Land, J. M., Rahman, S., & Hargreaves, I. P. (2014). Effect of Coenzyme Q10 supplementation on mitochondrial electron transport chain activity and mitochondrial oxidative stress in Coenzyme Q10 deficient human neuronal cells. The International Journal of Biochemistry & Cell Biology, 50, 60-3. https://doi.org/10.1016/j.biocel.2014.02.003
Duberley KE, et al. Effect of Coenzyme Q10 Supplementation On Mitochondrial Electron Transport Chain Activity and Mitochondrial Oxidative Stress in Coenzyme Q10 Deficient Human Neuronal Cells. Int J Biochem Cell Biol. 2014;50:60-3. PubMed PMID: 24534273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Coenzyme Q10 supplementation on mitochondrial electron transport chain activity and mitochondrial oxidative stress in Coenzyme Q10 deficient human neuronal cells. AU - Duberley,K E, AU - Heales,S J R, AU - Abramov,A Y, AU - Chalasani,A, AU - Land,J M, AU - Rahman,S, AU - Hargreaves,I P, Y1 - 2014/02/15/ PY - 2013/09/28/received PY - 2014/01/28/revised PY - 2014/02/07/accepted PY - 2014/2/19/entrez PY - 2014/2/19/pubmed PY - 2015/7/16/medline KW - Coenzyme Q(10) KW - Mitochondrial electron transport chain KW - Mitochondrial membrane potential KW - Neuronal KW - Reactive oxygen species SP - 60 EP - 3 JF - The international journal of biochemistry & cell biology JO - Int J Biochem Cell Biol VL - 50 N2 - Primary Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with a heterogeneous clinical presentation. Common presenting features include both muscle and neurological dysfunction. Muscle abnormalities can improve, both clinically and biochemically following CoQ10 supplementation, however neurological symptoms are only partially ameliorated. At present, the reasons for the refractory nature of the neurological dysfunction remain unknown. In order to investigate this at the biochemical level we evaluated the effect of CoQ10 treatment upon a previously established neuronal cell model of CoQ10 deficiency. This model was established by treatment of human SH-SY5Y neuronal cells with 1 mM para-aminobenzoic acid (PABA) which induced a 54% decrease in cellular CoQ10 status. CoQ10 treatment (2.5 μM) for 5 days significantly (p<0.0005) decreased the level of mitochondrial superoxide in the CoQ10 deficient neurons. In addition, CoQ10 treatment (5 μM) restored mitochondrial membrane potential to 90% of the control level. However, CoQ10 treatment (10 μM) was only partially effective at restoring mitochondrial electron transport chain (ETC) enzyme activities. ETC complexes II/III activity was significantly (p<0.05) increased to 82.5% of control levels. ETC complexes I and IV activities were restored to 71.1% and 77.7%, respectively of control levels. In conclusion, the results of this study have indicated that although mitochondrial oxidative stress can be attenuated in CoQ10 deficient neurons following CoQ10 supplementation, ETC enzyme activities appear partially refractory to treatment. Accordingly, treatment with >10 μM CoQ10 may be required to restore ETC enzyme activities to control level. Accordingly, these results have important implication for the treatment of the neurological presentations of CoQ10 deficiency and indicate that high doses of CoQ10 may be required to elicit therapeutic efficacy. SN - 1878-5875 UR - https://www.unboundmedicine.com/medline/citation/24534273/Effect_of_Coenzyme_Q10_supplementation_on_mitochondrial_electron_transport_chain_activity_and_mitochondrial_oxidative_stress_in_Coenzyme_Q10_deficient_human_neuronal_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357-2725(14)00046-6 DB - PRIME DP - Unbound Medicine ER -