Targeted Antioxidants in Exercise-Induced Mitochondrial Oxidative Stress: Emphasis on DNA Damage

Abstract

Exercise simultaneously incites beneficial (e.g., signal) and harming (e.g., damage to macromolecules) effects, likely through the generation of reactive oxygen and nitrogen species (RONS) and downstream changes to redox homeostasis. Given the link between nuclear DNA damage and human longevity/pathology, research attempting to modulate DNA damage and restore redox homeostasis through non-selective pleiotropic antioxidants has yielded mixed results. Furthermore, until recently the role of oxidative modifications to mitochondrial DNA (mtDNA) in the context of exercising humans has largely been ignored. The development of antioxidant compounds which specifically target the mitochondria has unveiled a number of exciting avenues of exploration which allow for more precise discernment of the pathways involved with the generation of RONS and mitochondrial oxidative stress. Thus, the primary function of this review, and indeed its novel feature, is to highlight the potential roles of mitochondria-targeted antioxidants on perturbations to mitochondrial oxidative stress and the implications for exercise, with special focus on mtDNA damage. A brief synopsis of the current literature addressing the sources of mitochondrial superoxide and hydrogen peroxide, and available mitochondria-targeted antioxidants is also discussed.

MitoQ Is Able to Modulate Apoptosis and Inflammation

“…MTAs are indeed known for their activity against the activation of the mitochondrial damage because of their antioxidant and mitochondrial protective properties. In particular, MitoQ is characterized by high bioavailability, and several prior studies have demonstrated its neuroprotective potential [ 4 , 5 ].…”

Preventive effects of garlic and lemon extract combined with aerobic exercise on blood metabolic parameters and liver enzymes

“…Aerobic exercise increases the efficiency of energy production systems and cardiorespiratory resistance. However, this exercise methodology performed at high intensities also increases the level of oxidative stress (Aslani et al, 2015), which can damage cellular DNA from various sources (Williamson and Davison, 2020). Oxidative stress plays a key role in obesity, and associated conditions such as dyslipidemia and hypertension, which are also risk factors for CVD (Marseglia et al, 2014).…”

The Acute Effects of Exercise and Temperature on Regional mtDNA

“…These data suggest a greater loss of MAJ copy numbers after exercise within the heat (33 °C). Theoretically, these reduced copy numbers are based upon the instability of the MAJ because of its unprotected location within the plasmid during the replication processes brought on by the stress of exercise and temperature [ 9 , 29 ]. Consistent reductions in mtDNA copy number have been demonstrated after a bout of moderate or high intensity exercise [ 18 , 19 , 27 , 28 ].…”

“…The MAJ region encodes for most of the proteins directly responsible for ATP production via oxidative phosphorylation [ 9 , 29 ] and thus may have profound bioenergetics implications. mtDNA reductions have been previously explained by an increased production of ROS with acute exercise (during and 4 h post-exercise) contributing to increased mtDNA damage [ 9 , 18 , 19 , 29 ].…”