Mitochondrially-targeted treatment strategies
Luiz H.M.Bozia Molecular Aspects of Medicine Volume 71, February 2020, 100836
Disruption of mitochondrial function is a common feature of inherited mitochondrial diseases (mitochondriopathies) and many other infectious and non-infectious diseases including viral, bacterial and protozoan infections, inflammatory and chronic pain, neurodegeneration, diabetes, obesity and cardiovascular diseases. Mitochondria therefore become an attractive target for developing new therapies. In this review we describe critical mechanisms involved in the maintenance of mitochondrial functionality and discuss strategies used to identify and validate mitochondrial targets in different diseases. We also highlight the most recent preclinical and clinical findings using molecules targeting mitochondrial bioenergetics, morphology, number, content and detoxification systems in common pathologies.
Coenzyme Q10 (CoQ10) supplementation is a mitochondrially-untargeted adjuvant intervention that indirectly affects mitochondrial oxidative stress. CoQ10 is a component of ETC that mediates electron transport from complexes I and II to complex III. Its reduced form, ubiquinol, has an antioxidant effect inside the organelle (Kelso et al., 2001; Kiyuna et al., 2018). CoQ10 supplementation attenuates oxidative stress and cardiomyocyte remodeling in rodents with diabetic cardiomyopathy (De Blasio et al., 2015). Treatment of heart failure patients with CoQ10 reduces the number of adverse cardiovascular events and rates of hospitalization and mortality (Mortensen et al., 2014). In addition, there are other antioxidant compounds with potential to treat cardiovascular diseases, including radical scavengers (Edaravone, XJB-5-131) and SOD mimetics (EUK8, M40403, Me2DO2A, MnTBPA) (Kiyuna et al., 2018).
Similarly, administration of CoQ10 mitigates the progression of obesity and type 2 diabetes in mice (Xu et al., 2017). CoQ10 has been tested in Phase III clinical trials in patients with dyslipidemia (NCT02407548 (Zhang et al., 2018b)) and type 2 diabetes (IRCT138806102394N1 (Zahedi et al., 2014)). CoQ10 ameliorates multiple cardiovascular risk factors in patients with dyslipidemia (Zhang et al., 2018b) and improves glycemic control in type 2 diabetic patients (Zahedi et al., 2014).
