The role of mitochondria in SAMS

Allard, Neeltje; Timmers, Silvie


In this chapter we summarize the evidence for a central role of mitochondrial dysfunction in statin-associated muscle symptoms. Statin-related mitochondrial dysfunction can manifest itself in skeletal muscle by inducing a plethora of architectural and biochemical adaptations. Structural changes seen in biopsy specimens, including red ragged fibers, cytochrome oxidase-negative myofibers, and lipid-loaded vacuoles, are signs of mitochondrial respiratory chain dysfunction. Disturbances in mitochondrial energy metabolism are shown through increased lactate/pyruvate ratios, disruption of beta-oxidation, a decrease in mitochondrial DNA, and disturbances in electron transport chain complex activities. Apoptosis of myofibers may occur as a result of mitochondrial-mediated apoptosis and the formation of reactive oxygen species. Furthermore the role of coenzyme Q10 deficiency and disturbances in calcium homeostasis in relation to statin-induced mitochondrial dysfunction will be discussed.