title: The role of mitochondria in statin-induced myopathy.
abstract: BACKGROUND
  Statins inhibit hydroxymethylglutaryl-coenzyme A reductase, decrease plasma low-density lipoprotein cholesterol and reduce cardiovascular morbidity and mortality. They can also exert adverse effects, mostly affecting skeletal muscle, ranging from mild myalgia to rhabdomyolysis.
  
  
  METHODS
  Based on a PubMed search until December 2014, this review summarizes studies on statin effects on muscle mitochondrial morphology and function in the context of myopathy.
  
  
  RESULTS
  Possible mechanisms of statin-induced myopathy include lower cholesterol synthesis and production of prenylated proteins, reduced dolichols and increased atrogin-1 expression. Statin-treated patients frequently feature decreased muscle coenzyme Q10 (CoQ10) contents, suggesting that statins might impair mitochondrial function. In cell cultures, statins diminish muscle oxygen consumption, promote mitochondrial permeability transient pore opening and generate apoptotic proteins. Animal models confirm the statin-induced decrease in muscle CoQ10, but reveal no changes in mitochondrial enzyme activities. Human studies yield contradictory results, with decreased CoQ10, elevated lipids, decreased enzyme activities in muscle and impaired maximal oxygen uptake in several but not all studies. Some patients are susceptible to statin-induced myopathy due to variations in genes encoding proteins involved in statin uptake and biotransformation such as the solute carrier organic anion transporter family member 1B1 (SLCO1B1) or cytochrome P450 (CYP2D6, CYP3A4, CYP3A5). Carriers for carnitine palmitoyltransferase II deficiency and McArdle disease also present with higher prevalence of statin-induced myopathy.
  
  
  CONCLUSIONS
  Despite the widespread use of statins, the pathogenesis of statin-induced myopathy remains unclear, requiring prospective randomized controlled trials with intensive phenotyping also for identifying strategies for its risk assessment, prevention and treatment.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Apostolopoulou
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari (DISFeB), Università degli Studi di Milano, Milan, Italy.|IRCCS Multimedica, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Corsini
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects; D009135:Muscular Diseases / Q000139:chemically induced*; D011817:Rabbits; D051381:Rats; D012307:Risk Factors; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014451:Ubiquinone; C024989:coenzyme Q10
keywords: Mitochondria; myopathy; skeletal muscle; statins; ubiquinone