Coenzyme Q10 Reverses Mitochondrial Dysfunction in Atorvastatin-Treated Mice and Increases Exercise Endurance

J Appl Physiol (1985). 2012 Aug;113(3):479-86. doi: 10.1152/japplphysiol.01362.2011. Epub 2012 May 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin
  • Heptanoic Acids / antagonists & inhibitors
  • Heptanoic Acids / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lactic Acid / biosynthesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria, Muscle / drug effects*
  • Muscle Cells / drug effects
  • Muscle Strength / drug effects
  • Muscle, Skeletal / anatomy & histology
  • Muscle, Skeletal / drug effects
  • Organ Size / drug effects
  • Oxygen Consumption / drug effects
  • Physical Conditioning, Animal / physiology*
  • Physical Endurance / drug effects*
  • Pravastatin / pharmacology
  • Pyrroles / antagonists & inhibitors
  • Pyrroles / pharmacology*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / analysis
  • Ubiquinone / pharmacology

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Ubiquinone
  • Lactic Acid
  • Atorvastatin
  • coenzyme Q10
  • Pravastatin