Coenzyme Q 10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance

Ayako Muraki, Kazutoshi Miyashita, Masanori Mitsuishi, Masanori Tamaki, Kumiko Tanaka, Hiroshi Itoh

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Statins are cholesterollowering 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 (HMGCoA) 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 reductasedependent 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 atorvastatintreated 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 atorvastatinrelated mitochondrial dysfunction and decrease in exercise tolerance.

Original languageEnglish
Pages (from-to)479-486
Number of pages8
JournalJournal of Applied Physiology
Volume113
Issue number3
DOIs
Publication statusPublished - 2012 Aug 1

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Ubiquinone
Pravastatin
Muscle Cells
Oxygen
Exercise Tolerance
Coenzymes
Terpenes
Muscle Strength
Muscular Diseases
Electron Transport
LDL Cholesterol
Energy Metabolism
Atorvastatin Calcium
Lactic Acid
Oxidoreductases
Cardiovascular Diseases
Pharmaceutical Preparations
Coenzyme Q10 Deficiency

Keywords

  • Coenzyme Q
  • Exercise
  • Mitochondria
  • Oxygen utilization
  • Statins

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Medicine(all)

Cite this

Coenzyme Q 10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance. / Muraki, Ayako; Miyashita, Kazutoshi; Mitsuishi, Masanori; Tamaki, Masanori; Tanaka, Kumiko; Itoh, Hiroshi.

In: Journal of Applied Physiology, Vol. 113, No. 3, 01.08.2012, p. 479-486.

Research output: Contribution to journalArticle

Muraki, Ayako ; Miyashita, Kazutoshi ; Mitsuishi, Masanori ; Tamaki, Masanori ; Tanaka, Kumiko ; Itoh, Hiroshi. / Coenzyme Q 10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance. In: Journal of Applied Physiology. 2012 ; Vol. 113, No. 3. pp. 479-486.
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