• MITOQ
  • ANTIOXIDANT SCIENCE

How does MitoQ work – the MitoQ mechanism of action.

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Our tiny but complex cells are the fundamental units of life, and we are made of over 37 trillion of them! So, naturally, keeping our body in optimal condition means we need to pay close attention to our cells and their health. Deep within our cells sit the mitochondria, these little factories are constantly churning out energy for us to use, but while doing so they also pump out free radicals. Too many free radicals can cause oxidative stress making it harder for our cells to carry out their jobs and keep you healthy.

This is where antioxidants come in, molecules that remove free radicals and keep our cellular machinery running smoothly. But for antioxidants to be effective, they have to reach the source of oxidative stress, the mitochondria.

This is what makes MitoQ stand out from the rest. MitoQ (Mitoquinol Mesylate) is the world’s first mitochondrially-targeted antioxidant. Unlike regular antioxidants, MitoQ’s unique structure allows it to easily enter the mitochondria, where it can start to tackle free radicals at the source. This potent antioxidant ability means that MitoQ can help protect the cell from oxidative stress and reduce both structural and DNA damage. By rejuvenating cell health, MitoQ has been shown to help improve sport and exercise performance, cardiovascular health, and promote healthier ageing.

Okay so that sounds promising, but what is MitoQ really doing inside of the cell? Read on below to learn about the MitoQ mechanism of action.

Graph of antioxidants declining

Cells need antioxidants

Your body is made almost entirely of cells, approximately 37.5 trillion of them, and mitochondria give cells their functional energy, signaling, and much more. In fact, mitochondria are responsible for producing 95% of the body's energy (ATP). During the production of ATP, free radicals are made as a by-product. These molecules are missing an electron from their outer shell making them highly reactive and unstable. To regain stability, free radicals steal electrons from cellular structures and if they accumulate in excess, can cause oxidative damage to mitochondria. This damage can disrupt the way our mitochondria function and their structure, meaning that free radicals can leak out of the mitochondria and into the rest of the cell where they can cause even more damage1.

Our body has a counterattack to protect itself from these free radicals: antioxidants. Antioxidants act as sacrificial molecules, donating electrons to free radicals and preventing them from stealing electrons from important cellular structures. In healthy, unstressed cells, the free radical- to- antioxidant ratio is balanced meaning there are enough antioxidants to keep free radicals under control. However, if the antioxidant ability of the cell is lower than the number of free radicals, the cell can gradually move into a state known as ‘oxidative stress’ or ‘cell stress’. Given that your body is made of cells, oxidative stress can play a damaging role in your health and energy levels.

Unfortunately, as we age, our natural levels of antioxidants start to decline, and additionally, our modern world can also expose us to things that stress our cells such as environmental toxins, poor sleep habits, unhealthy diets, and mental stress. This is why supplementing with antioxidants daily is important.

However, to be the most useful, antioxidants need to be able to neutralize free radicals at their source, within the mitochondria. That’s not easy, because the mitochondria’s double wall doesn’t let much pass through it. What’s required is a small, cell-targeted antioxidant: MitoQ.

Difference between MitoQ and CoQ10

Structure of MitoQ

One of the key antioxidants your body produces inside the mitochondria to control free radicals is CoQ10. MitoQ is an advanced, modified form of CoQ10 that is bio-designed to be smaller and is positively charged so it can easily pass through the mitochondrial wall. MitoQ is made of three main parts, each with key functions:

1. The active site of MitoQ is its antioxidant head. This is the same as in CoQ10 and is the part of the molecule that neutralizes free radicals.

2. Attached to the antioxidant head is the carbon chain made of 10 repeating units. This chain is much shorter in MitoQ than it is in CoQ10, which improves its absorption.

3. At the base of MitoQ is a positive charge that electrochemically pulls MitoQ through cells into the negatively charged inner mitochondrial wall, where its antioxidant powers are released.

MitoQ being absorbed into the cell

How is MitoQ absorbed?

Unlike the regular antioxidant CoQ10, which requires food to be absorbed, MitoQ is water-soluble and is best taken on an empty stomach. After being swallowed, MitoQ is quickly absorbed into the bloodstream in approximately 30 minutes2. Once in the bloodstream, MitoQ is rapidly transported to different organ tissues. MitoQ primarily accumulates in tissues with high-energy requirements like the heart, liver, skeletal muscle, and brain. Thanks to its positive charge, MitoQ can pass through all biological membranes3, including the blood-brain barrier4.

Most supplements, including many regular antioxidants, have a hard time entering the mitochondria as these organelles are tightly regulated and have a double wall. However, this isn’t an issue for MitoQ and once inside your cells, MitoQ is quickly drawn into the mitochondria thanks to its positive charge. Cell studies suggest that this happens within 20-40 minutes2,5.

Mitoquinol mesylate mechanism of action diagram

What does MitoQ do in the cell?

MitoQ has multiple actions within the mitochondria and the cell itself. By combating free radicals MitoQ helps mitigate oxidative stress by reducing free radical and DNA damage therefore supporting healthy mitochondrial function.

Once it enters the mitochondria, MitoQ's unique structure helps it stick into place. The positive tail attaches to the inner mitochondrial wall5 which keeps it anchored, while the antioxidant head is free to get to work on neutralizing free radicals. By being attached in this location, MitoQ helps to protect the wall against free radical damage.

This inner wall is folded and has a large surface area that’s about 5x greater than the outer wall. This makes it an ideal place for MitoQ, as it means it can cover a large area through the internal surface of the mitochondria.

Once it has neutralized a free radical, MitoQ has a unique ability to renew itself. Meaning one molecule of MitoQ can be used repeatedly to neutralize many free radicals. Once the active form of MitoQ (mitoquinol) neutralizes a free radical, it is oxidized to mitoquinone. Mitoquinone is then converted back to the active mitoquinol form by the mitochondria’s electron transport chain, restoring its antioxidant ability. This recycling property is one of the reasons that MitoQ is such a strong antioxidant.

Controlling free radicals

Free radicals are tricky as they’re both a good thing (in small amounts) and a bad thing (in excess). They’re a by-product of the energy-creation process within the mitochondria and in small amounts, they are important signaling molecules. But when the balance tips and they’re in excess, free radical build up can cause oxidative stress, the main contributor to cell stress. Signs of oxidative stress in the cell can include the disruption of the cell membrane, DNA damage, and protein degradation. All of these features are detrimental to cell health and can even lead to premature cell death.

MitoQ significantly reduces free radicals within the mitochondria to reduce oxidative stress and return balance to the cell6-8. Not only does MitoQ remove free radicals on it’s own, it can also encourage the production of our own internal antioxidant enzymes like catalase that breaks down harmful hydrogen peroxide6.

By scavenging free radicals, MitoQ works as a tool to control oxidative stress8. Keeping free radicals in equilibrium means that you can live a fast-paced life knowing that your cells are creating cleaner energy to support you physically, mentally, and emotionally.

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What effect does MitoQ have on the body?

Energy

As you know, energy production starts within the cell, specifically the mitochondria. This complex hub takes the metabolites from the food we eat and converts them into usable cellular energy to fuel our physical, mental, and emotional operations. Unfortunately, this process creates free radicals which, in excess, can damage the mitochondria, leading to energy disruption. This can be made worse by age and our modern lifestyles which often expose our bodies to unhealthy diets and sedentary habits.

Your cells need a lot of energy to carry you through the day. This can be a big ask when life gets hectic and your energy gets spent trying to keep up. Pressure to handle a busy household, nurture your kids, and meet tight work deadlines can pile up quickly, leaving little energy left in the tank for you and your body. In order for your body to keep up with the energy demands of modern life, you’ve got to take care of your energy engine.

Your engine’s machinery is both intricate and delicate and it sits in a part of the mitochondria that is often damaged by oxidative stress. MitoQ works to aid energy production by supporting mitochondrial health and energy production and may also work to improve energy allocation through improved insulin and glucose signaling.

Heart Health

Our cardiovascular system is what pumps blood around our body, delivering oxygen and nutrients to our tissues. This complex system includes the heart that sits in our chest and provides the force needed to circulate the blood through some 60,000 miles of connecting blood vessels. The largest of these blood vessels is the aorta which carries all of the blood away from the heart, sending it throughout the body.

This system is particularly sensitive to oxidative stress, especially as we age. One major target of oxidative stress is the endothelium which lines our blood vessels and is responsible for controlling vasodilation and vasoconstriction i.e., the widening and narrowing of our blood vessels. Endothelial-dependent dilation (EDD) is a key measure of assessing heart health in the elderly and as we age, EDD can be inhibited, causing a narrowing of blood vessels.

MitoQ has been shown to improve EDD by reducing oxidized LDL-cholesterol within blood vessels, allowing for the release of nitric oxide (NO) an important vasodilator19. In a study published by the American Heart Association; six weeks of 20mg/day MitoQ has been shown to reduce oxidized LDL cholesterol by up to 13%, improving vasodilation by up to 42%20. This study also found that MitoQ improved aortic stiffening; a common biomarker associated with aging that is difficult to reverse.

Exercise Performance

Mitochondria generate 95% of the body's energy and therefore mitochondrial health is crucial for optimal athletic performance. The mitochondria in the muscles of trained athletes are denser than untrained individuals, and athletes generally have upregulated pathways associated with mitochondrial biogenesis and fusion21. Supplementing with antioxidants is often a common strategy for improving athletic performance, as increased energy expenditure can lead to an increase in free radical production.

There have been numerous human clinical trials investigating the effects of MitoQ on athletic performance; with positive impacts seen in peak power, mobility, and oxygen uptake. In trained cyclists, taking 20mg of MitoQ over four weeks increased their muscles peak power output by up to 4.4%, leading to a 10.8-second reduction in finishing times8. In a similar clinical trial, an increase in peak power at VO2 max was also seen after just 10 days of 20 mg MitoQ supplementation22.

In humans, MitoQ has also been shown to work synergistically with exercise to upregulate several molecular pathways associated with mitochondrial biogenesis22, the reduction of inflammation7, and promoting blood vessel formation (angiogenesis)22.

Healthy Ageing

Mitochondrial function is essential for healthy aging. As we age, our mitochondria can accumulate damage from free radicals, and fail to generate energy as efficiently as they once did. Preclinical studies of MitoQ have shown that by reducing mitochondrial oxidative stress, MitoQ may encourage healthy aging.

In one pre-clinical study, MitoQ has been found to protect against age-associated memory loss by increasing ATP and preserving synaptic mitochondrial function of the hippocampus23. In human fibroblasts MitoQ has been shown to counteract telomere shortening under oxidative stress24 and in a study on C. elegans, MitoQ was shown to improve health-span partly by maintaining mitochondrial membrane integrity25.

Is MitoQ safe?

MitoQ has undergone extensive safety and toxicity testing in both animals and humans. Clinical studies at 20 mg of MitoQ show excellent safety, and acute doses of MitoQ have shown kidney safety at high levels 100-160mg. MitoQ Ltd. has independently reviewed the scientific data as self-affirmed GRAS (Generally Regarded as Safe).

MitoQ Research

More than 20 clinical trials have been published on MitoQ, and over 30 clinical trials are currently underway or in the planning stage. To date, there are over 760 peer-reviewed publications researching or reviewing MitoQ. Too see MitoQ’s larger bibliography check out our research page.

MitoQ research

REFERENCES

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    Smith, R. A. J., Hartley, R. C., Cochemé, H. M. & Murphy, M. P. Mitochondrial pharmacology. Trends in Pharmacological Sciences 33, 341–352 (2012).

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    Zhang, J. et al. MitoQ ameliorates testis injury from oxidative attack by repairing mitochondria and promoting the Keap1-Nrf2 pathway. Toxicology and Applied Pharmacology 370, 78–92 (2019).

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    Smith, R. A. J., Porteous, C. M., Gane, A. M. & Murphy, M. P. Delivery of bioactive molecules to mitochondria in vivo. Proceedings of the National Academy of Sciences 100, 5407–5412 (2003).

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    Salvi, A., Liu, H. & Salim, S. Involvement of oxidative stress and mitochondrial mechanisms in air pollution-related neurobiological impairments. Neurobiology of Stress 12, 100205 (2020).

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    Kelso, G. F. et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem 276, 4588–4596 (2001).

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    Pham, T. et al. MitoQ and CoQ10 supplementation mildly suppresses skeletal muscle mitochondrial hydrogen peroxide levels without impacting mitochondrial function in middle-aged men. Eur J Appl Physiol 120, 1657–1669 (2020).

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    Park, Y. et al. MitoQ supplementation improves oxygen uptake kinetic by reduced reactive oxygen species levels and altered expression of miR-155 and miR-181b. The FASEB Journal 36, (2022).

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    Broome, S. C., Braakhuis, A. J., Mitchell, C. J. & Merry, T. L. Mitochondria-targeted antioxidant supplementation improves 8 km time trial performance in middle-aged trained male cyclists. Journal of the International Society of Sports Nutrition 18, 58 (2021).

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    Ning, R. et al. The mitochondria-targeted antioxidant MitoQ attenuated PM2.5-induced vascular fibrosis via regulating mitophagy. Redox Biol 46, 102113 (2021).

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    Jelinek, A. et al. Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Free Radical Biology and Medicine 117, 45–57 (2018).

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    Lyamzaev, K. G., Panteleeva, A. A., Simonyan, R. A., Avetisyan, A. V. & Chernyak, B. V. Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis. Cells 12, 611 (2023).

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    Mazhar, M. et al. Implication of ferroptosis in aging. Cell Death Discov 7, 149 (2021).

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    Li, C., Liu, J., Hou, W., Kang, R. & Tang, D. STING1 Promotes Ferroptosis Through MFN1/2-Dependent Mitochondrial Fusion. Front Cell Dev Biol 9, 698679 (2021).

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    Liang, Z. et al. Epothilone B inactivation of Sirtuin1 promotes mitochondrial reactive oxygen species to induce dysfunction and ferroptosis of Schwann cells. European Journal of Pharmaceutical Sciences 181, 106350 (2023).

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    Merkel, M. et al. Mitochondrial Reactive Oxygen Species Formation Determines ACSL4/LPCAT2-Mediated Ferroptosis. Antioxidants (Basel) 12, 1590 (2023).

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    Feniouk, B. A. & Skulachev, V. P. Cellular and Molecular Mechanisms of Action of Mitochondria-Targeted Antioxidants. Current Aging Science 10, 41–48.

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    López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The Hallmarks of Aging. Cell 153, 1194–1217 (2013).

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    Williamson, J., Hughes, C. M., Cobley, J. N. & Davison, G. W. The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage. Redox Biology 36, 101673 (2020).

  • 19.

    Murray, K. O. et al. Chronic mitochondria antioxidant treatment in older adults alters the circulating milieu to improve endothelial cell function and mitochondrial oxidative stress. American Journal of Physiology-Heart and Circulatory Physiology (2023) doi:10.1152/ajpheart.00270.2023.

  • 20.

    Rossman, M. J. et al. Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertension 71, 1056–1063 (2018).

  • 21.

    Botella, J. et al. Increased mitochondrial surface area and cristae density in the skeletal muscle of strength athletes. The Journal of Physiology 601, 2899–2915 (2023).

  • 22.

    Broome, S. C. et al. MitoQ supplementation augments acute exercise-induced increases in muscle PGC1α mRNA and improves training-induced increases in peak power independent of mitochondrial content and function in untrained middle-aged men. Redox Biology 53, 102341 (2022).

  • 23.

    Olesen, M. A., Torres, A. K., Jara, C., Murphy, M. P. & Tapia-Rojas, C. Premature synaptic mitochondrial dysfunction in the hippocampus during aging contributes to memory loss. Redox Biology 34, 101558 (2020).

  • 24.

    Saretzki, G., Murphy, M. P. & Von Zglinicki, T. MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress. Aging Cell 2, 141–143 (2003).

  • 25.

    Ng, L. F. et al. The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease. Free Radical Biology and Medicine 71, 390–401 (2014).

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