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Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance.
J Appl Physiol (1985). 2012 Aug; 113(3):479-86.JA

Abstract

Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.

Authors+Show Affiliations

Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22653988

Citation

Muraki, Ayako, et al. "Coenzyme Q10 Reverses Mitochondrial Dysfunction in Atorvastatin-treated Mice and Increases Exercise Endurance." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 113, no. 3, 2012, pp. 479-86.
Muraki A, Miyashita K, Mitsuishi M, et al. Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance. J Appl Physiol (1985). 2012;113(3):479-86.
Muraki, A., Miyashita, K., Mitsuishi, M., Tamaki, M., Tanaka, K., & Itoh, H. (2012). Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance. Journal of Applied Physiology (Bethesda, Md. : 1985), 113(3), 479-86. https://doi.org/10.1152/japplphysiol.01362.2011
Muraki A, et al. Coenzyme Q10 Reverses Mitochondrial Dysfunction in Atorvastatin-treated Mice and Increases Exercise Endurance. J Appl Physiol (1985). 2012;113(3):479-86. PubMed PMID: 22653988.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance. AU - Muraki,Ayako, AU - Miyashita,Kazutoshi, AU - Mitsuishi,Masanori, AU - Tamaki,Masanori, AU - Tanaka,Kumiko, AU - Itoh,Hiroshi, Y1 - 2012/05/31/ PY - 2012/6/2/entrez PY - 2012/6/2/pubmed PY - 2013/1/9/medline SP - 479 EP - 86 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J Appl Physiol (1985) VL - 113 IS - 3 N2 - Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance. SN - 1522-1601 UR - https://www.unboundmedicine.com/medline/citation/22653988/Coenzyme_Q10_reverses_mitochondrial_dysfunction_in_atorvastatin_treated_mice_and_increases_exercise_endurance_ L2 - https://journals.physiology.org/doi/10.1152/japplphysiol.01362.2011?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -