The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage.

Josh Williamson, Ciara M Hughes, James N Cobley, Gareth W Davison

Journal: Redox biology 2021;36():101673

PMID: 32810739

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Plain Language Summary

Mitochondria have an established role in the life cycle of a cell, contributing to cellular networks aligned to metabolism, biosynthetic pathways, and apoptotic cell death. Exercise increases the univalent reduction of ground state molecular dioxygen to superoxide in skeletal muscle. The aim of this study was to determine whether (1) a bout of high-intensity intermittent exercise (HIIE) damaged mitochondrial (mt)DNA; and (2) Mitoquinone (MitoQ) [orally available mitochondrial-targeted coenzyme Q10] could prevent mtDNA damage. This study is a double-blind, randomized, placebo-controlled design. Twenty-four (n = 24) healthy, recreationally active males volunteered to take part in the study. The participants were allocated to two groups: MitoQ (n = 12) and placebo (n = 12), and subsequently took part in a two-phased supplementation trial. Results showed that: - exercise increased DNA damage in nucleus and mitochondria. In fact, HIIE damages mtDNA both systemically in lymphocytes and locally in muscle tissue, occurring in parallel with nuclear DNA damage. - chronic MitoQ supplementation offers a prophylactic effect. - MitoQ decreases exercise-induced DNA damage. Authors conclude that the notion that a protective effect of a mitochondria-targeted antioxidant is only unmasked by exercise, reinforces the value of interrogating multiple physiological states when appraising the efficacy of an antioxidant.

Abstract

High-intensity exercise damages mitochondrial DNA (mtDNA) in skeletal muscle. Whether MitoQ - a redox active mitochondrial targeted quinone - can reduce exercise-induced mtDNA damage is unknown. In a double-blind, randomized, placebo-controlled design, twenty-four healthy male participants consisting of two groups (placebo; n = 12, MitoQ; n = 12) performed an exercise trial of 4 x 4-min bouts at 90-95% of heart rate max. Participants completed an acute (20 mg MitoQ or placebo 1-h pre-exercise) and chronic (21 days of supplementation) phase. Blood and skeletal muscle were sampled immediately pre- and post-exercise and analysed for nuclear and mtDNA damage, lipid hydroperoxides, lipid soluble antioxidants, and the ascorbyl free radical. Exercise significantly increased nuclear and mtDNA damage across lymphocytes and muscle (P < 0.05), which was accompanied with changes in lipid hydroperoxides, ascorbyl free radical, and α-tocopherol (P < 0.05). Acute MitoQ treatment failed to impact any biomarker likely due to insufficient initial bioavailability. However, chronic MitoQ treatment attenuated nuclear (P < 0.05) and mtDNA damage in lymphocytes and muscle tissue (P < 0.05). Our work is the first to show a protective effect of chronic MitoQ supplementation on the mitochondrial and nuclear genomes in lymphocytes and human muscle tissue following exercise, which is important for genome stability.

Address: Ulster University, Sport and Exercise Research Institute, Newtownabbey, Northern Ireland, UK.; Ulster University, Nursing and Health Research Institute, Newtownabbey, Northern Ireland, UK.; Free Radical Research Group, University of the Highlands and Islands, Centre for Health Sciences, Inverness, IV2 3JH, UK.; Ulster University, Sport and Exercise Research Institute, Newtownabbey, Northern Ireland, UK. Electronic address: [email protected].

DOI: 10.1016/j.redox.2020.101673

Patient Centred Factor

Mediators: Mitochondria

Clinical Imbalances

Immune and inflammation Structural Integrity and Musculoskeletal

Laboratory Testing

Blood Tissue biopsy Imaging

Modifiable Lifestyle Factors

Diet Exercise and movement

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Exercise Antioxidant Lipid Coenzyme Q10

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/antioxidants.html

MeSH Terms: Antioxidants, DNA, Mitochondrial, Double-Blind Method, Humans, Male, Mitochondria, Organophosphorus Compounds, Oxidative Stress, Reactive Oxygen Species, Ubiquinone