Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of
insulin resistance, and abnormalities in
fatty acid metabolism. As a consequence,
mitochondrial dysfunction contributes to the pathophysiology of
insulin resistance,
obesity, diabetes,
vascular disease, and chronic
heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted
therapies. We review the current knowledge of the contribution of
mitochondrial dysfunction to
chronic diseases, the outcomes of experimental studies on mitochondrial-targeted
therapies, and explore the potential of metabolic modulators in the treatment of selected
chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of
L-carnitine and its analogues acetyl and propionyl
L-carnitine in several
chronic diseases.
L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in
fatty acid oxidation and energy metabolism. In addition to the transportation of
free fatty acids across the inner mitochondrial membrane,
L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus,
L-carnitine and its derivatives show promise in the treatment of
chronic conditions and diseases associated with
mitochondrial dysfunction but further translational studies are needed to fully explore their potential.