Małgorzata Belczyk, Małgorzata Elżbieta Knapik-Czajka, Anna Gawędzka, Jagoda Drąg

The effect of statins on mitochondria – current state of knowledge

 

 

2025-01-14

Introduction. Statins are the most commonly used class of drugs to treat and prevent cardiovascular diseases worldwide. Beyond their lipid-lowering activity, statins modulate multiple metabolic pathways in different tissues. Mitochondria are one of the most recognized cellular targets for statins.

Aim. The aim of this review was to summarize the current state of knowledge on the most recognized effects of statins on mitochondria, mainly in skeletal muscle, cardiac muscle, pancreas and liver.

Methods. The literature was reviewed by searching the scientific databases PubMed and Google Scholar. The search strategy included the following MeSH terms: “Statins” or “HMG-CoA Reductase Inhibitors” and “Mitochondria”, “Muscle” or “Myocytes”, “Cardiac muscle” or “Heart”, “Pancreas” or “Beta Cells”, Liver” or “Hepatocytes”. Human, animal and in vitro studies were included. The conference abstracts, letters, opinions, and editorials were excluded.

Results. Statins modify mitochondrial functions by affecting CoQ10 levels, reactive oxygen species (ROS) homeostasis, and mitochondrial oxidative metabolism as well as regulating the processes of mitophagy and ferroptosis. It has been proposed that depletion in muscle CoQ10 levels may be one of the factors involved in myotoxicity, the most frequent adverse effect of statins. Nowadays, there is no strong evidence of a direct association between muscular CoQ10 depletion and the development of Statin-Associated Muscle Symptoms (SAMS). Statins also modify ROS homeostasis, and their effect on ROS levels is tissue-specific. In skeletal muscle, statins induce high-oxidative stress, whereas in cardiac muscle, statins generate low-grade ROS levels and stimulate antioxidant capacity. In human skeletal muscle, statins impair mitochondrial oxidative metabolism, which may contribute to myotoxicity. In contrast, in cardiac muscle and liver, statins modifying oxidative metabolism prevent cardiac dysfunction and steatosis development. Dysfunction of mitochondrial metabolic pathways caused by statins results in inhibition of insulin secretion from -cells and stimulation of liver glucose production. Recent studies have demonstrated that statins may also regulate mitophagy and ferroptosis, but this issue needs to be further investigated.

Conclusion. Statins’ influence on mitochondria is complex and tissue-specific. Statins by distinct regulation of mitochondrial functions elicit either beneficial or adverse effects. Results of several studies indicate that in cardiac muscle, statins exert a cardioprotective effect, whereas their influence on skeletal muscle mitochondria is associated with myotoxicity. Dysregulation of mitochondrial metabolism in pancreatic b-cells and hepatocytes is one of the mechanisms of the diabetogenic effect of statins.

Keywords: Statins, mitochondria, metabolism, skeletal muscle, cardiac muscle.

© Farm Pol, 2024, 80(8): 579–587