Figure 4.

Possible targets of statins in the mitochondrion with deleterious effects on muscle function. The interaction of statins with muscle mitochondria can involve (i) reduced production of prenylated proteins including the mitochondrial electron transport chain (ETC) protein, ubiquinone (coenzyme Q10), (ii) subnormal levels of farnesyl pyrophosphate and geranylgeranyl pyrophosphate leading to impaired cell growth and autophagy, (iii) low membrane cholesterol content affecting membrane fluidity and ion channels, and (iv) the triggered calcium release from the sarcoplasmic reticulum via ryanodine receptors, resulting in impaired calcium signalling.^92–94 Statin-induced depletion of myocellular ubiquinone, an essential coenzyme which participates in electron transport during oxidative phosphorylation,⁹⁵ may attenuate electron transfer between complexes I, III, and II of ETC. ADP, adenosine diphosphate; ATP, adenosine triphosphate; Cyt C, cytochrome C; FAD, flavin adenine dinucleotide; FADH2, flavin adenine dinucleotide reduced; MPT, mitochondrial permeability transition; MtDNA, mitochondrial DNA; NAD, nicotinamide adenine dinucleotide; NADH, nicotinamide adenine dinucleotide; ROS, reactive oxidative species; TCA cycle, tricarboxylic acid cycle.