Statins and mitochondria

Abstract

The aim of this review is to report on the influence of statins on mitochondrial function. Statins are serum cholesterol-lowering drugs. They act by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the first committed enzyme of the mevalonate pathway. In this way, statins inhibit endogenous cholesterol synthesis. Emerging evidence suggests that statins impair mitochondria, demonstrated by abnormal mitochondrial morphology, decreased oxidative phosphorylation capacity and yield, decreased mitochondrial membrane potential, and activation of the intrinsic apoptotic pathway. The mechanisms of statin-induced mitochondrial dysfunction are not fully understood. The following causes are proposed: (i) deficiency of coenzyme Q10, an important electron carrier of the mitochondrial respiratory chain; (ii) inhibition of respiratory chain complexes; (iii) diminution of protein prenylation resulting from inhibition of the mevalonate pathway; and (iv) induction of the mitochondrial apoptosis pathway. These phenomena could play a significant role in the etiology of statin-induced diseases, especially myopathy. Studies on statin-induced mitochondrial apoptosis could be useful in developing a new cancer therapy.