What exactly is mitochondrial dysfunction -- and what does it mean for your daily life?
Mitochondria are highly important cellular organelles that require a nourished environment. In order to process energy substrates into molecular in the form of adenosine triphosphate (ATP), all conditions need to be in tip-top shape. You may remember, that the cells in the body are quite dependent on ATP, meaning these organelles live highly demanding lives.
Because of their important role in energy, mitochondria are under a lot of stress throughout the day; due to their high volumes of energy production, they also generate a lot of free radicals, which are damaging to cells. If these free radicals are not contained and removed, this can damage the way mitochondria process energy substrates and limit their capacity to produce energy.
Mitochondrial dysfunction is easy enough to understand, but it can mean many things. On one hand, it can be the consequence of a reduced number of functioning (or mature) mitochondria, contributing to a limited capacity for energy production.
On the other hand, it can reflect abnormal but necessary biochemical processes responsible for optimally functioning mitochondria, such as an inability to supplement mitochondria with substrates, or abnormalities in the way mitochondria process substrates to produce energy.
Biochemical overview of mitochondrial dysfunction
When mitochondria kick it into high gear, they produce an excess of nitric oxide (a free radical), which is normally removed by antioxidant compounds, which are known for their free radical scavenging activity. But let’s say the body lacks crucial vitamins such as C and E, or is suffering from lowered amounts of key antioxidant players. In this context, accumulated cellular nitric oxide results in a compound called peroxynitrite. As peroxynitrite levels increase, lipid peroxidation ensues, which is essentially the process of oxidizing molecules attacking lipids to break them apart.
Uncontrolled lipid peroxidation is dangerous because the cell membrane is almost entirely made of lipids. In the context of aberrant peroxidation, ruptured membranes and cell death may occur. This stimulates inflammatory molecules to increase their activity and can trigger an immune response, thereby elevating inflammation. Unfortunately the bad news doesn’t stop there, because inflammatory proteins like cytokines can also stimulate nitric oxide production, thereby generating a positive feedback system on cellular damage and increased free radical production.
The end result? You guessed it—mitochondrial dysfunction.
But similarly, as mentioned, nourishment is critical for mitochondria to perform adequately, so that energy demands are met throughout the day. If mitochondria do not have the molecular tools and protection necessary to produce energy, then mitochondrial dysfunction occurs, and you may be left feeling like a simple walk to the fridge is the hardest thing you’ve ever done.
Physical manifestations of mitochondrial dysfunction and how it relates to age
While there may not be concrete, telltale signs of mitochondrial dysfunction, there are some symptoms that are known to be driven by it. For example, fatigue is the single most important symptom to look out for when it comes to mitochondrial dysfunction. As we know, mitochondria are the “powerhouse of the cell” and are responsible for energy production. So accordingly, if mitochondria become impaired, their ability to produce energy is reduced, thereby resulting in low energy substrates (i.e. ATP) for the body to use and ultimately, feelings of fatigue and tiredness. This isn’t the fatigue you experience after a workout, however, and is much more noticeable as fatigue that sets in after completing mundane tasks like a walk to the bathroom or bending down to pick something up off the ground. If you just can't seem to wake up and perform normal tasks, this may be a sign of mitochondrial dysfunction.
Chronic diseases that involves prolonged inflammation and aging in general are two of the primary factors that contribute to the deterioration and dysfunction of mitochondria. It's been hypothesized that oxidative stress steadily increases over time as a result of the body trying to generate the same energy with aging materials. Think of it like trying to get the same level of power from a 10-year-old battery as you would get from a brand new, fully charged battery.
Under this hypothesis, the progressive increase in reactive oxygen species (ROS) and/or free radicals, contributes to permanently elevated levels of oxidative stress. And this recurring oxidative stress, in turn, damages cells increasingly more as ROS activity increases over time. In the end, you’re left with a highly oxidizing environment that is toxic to cells, which eventually causes these cells to die off and/or become senescent.
It may be possible to fend off the deleterious effects of aging if the proper steps are taken to prevent the accumulation of oxidative stress. At the same time, understanding the hallmarks of biological aging can also give you a leg up on tackling aging head on, so long as you’re willing to put in a bit of work and make some trips to your healthcare provider, of course.
Cellular energetics and the importance of CoQ10
To keep it simple, cellular energetics is just how energy is utilized by the body. More specifically, it is how the body captures energy through various energy sources (i.e. fats, carbohydrates, proteins) and breaks these sources down into constituents that can be burned to generate bodily fuel. A key component of cellular energetics is metabolic pathways, and in particular relevance to this article, energy generating processes like oxidative phosphorylation. This is the primary method that mitochondria use to generate energy in the form of ATP.
But this isn’t the whole story of cellular energetics. Small proteins called enzymes are required to facilitate the biochemical reactions that are necessary to break energy substrates down to form ATP. Enzymes are like the baking soda to your muffins—without it, it may take longer for the muffins to rise while baking in the oven. Baking soda helps any baked good to rise much faster while baking. Enzymes function similarly to baking soda in that they allow biochemical reactions to occur at faster than normal rates and are even required in some instances for certain reactions to happen.
One enzyme especially important to cellular energetics is Coenzyme Q10, or CoQ10.
A key function of mitochondria is the electron transport chain, which is where electrons are transferred following decomposition of energy substrates like carbohydrates or lipids to form ATP. CoQ10 is a critical enzyme found within the electron transport chain of mitochondria and functions as cofactor in the transfer of electrons as well as an antioxidant. It is also known to influence expression of genes responsible for cell signaling, cellular transport, and metabolism as well.
CoQ10 is directly involved in energy production because without it, the electron transport chain becomes impaired in its ability to transfer electrons in the formation of ATP. As a result, depletion of CoQ10 is likely to result in feelings of fatigue and weakness. In fact, studies have shown that supplementing CoQ10 in the diet can produce a modest increase in exercise capacity, an effect that is coupled by its ability to reduce blood pressure.
What’s more, administering CoQ10 to individuals with Parkinson’s disease was found to lower markers of oxidative damage in their cerebral spinal fluid, demonstrating direct effects of CoQ10 on oxidative stress, reflecting its antioxidant properties.
As CoQ10 is directly involved in the mitochondria’s ability to generate ATP, it is clear how low levels of CoQ10 may contribute to mitochondrial dysfunction.
This is why it is suggested that supplementation with CoQ10, especially in those who have reduced levels of this enzyme, will increase energy production and lower feelings of fatigue. Impressively, people who took CoQ10 supplements were able to work harder while experiencing less bouts of fatigue while exercising. Moreover, these same individuals found their recovery periods between workouts to be much shorter in comparison with individuals who took a placebo supplement.
Importantly, because some studies have reported reductions both in blood sugar and blood pressure following supplementation with CoQ10, those who have been diagnosed with metabolic or cardiovascular disorders should be wary before taking dietary CoQ10 and should consult their physician prior to use.
Mitochondrial dysfunction and disease
Overview of lipid peroxidation
Aging and oxidative stress theory
Electron transport chain