What is Mitochondrial Dysfunction?
The mitochondrion receives most recognition for its role in generating energy for cells in the body and they are commonly referred to as the powerhouse. Amazingly, the mitochondria in our cells have also generated a significant amount of attention from scientists and physicians in the most recent decade for its role in numerous other life processes.
The Role of Mitochondria
With the exception of red blood cells, mitochondria are unique organelles contained in every cell of the human body and contain its own DNA (6). Along with generating 90% of cellular energy in the form of ATP (adenosine triphosphate), mitochondria are involved in major metabolic functions of the human body. (7)
Mitochondria are found in varying concentrations in different tissues in the body and are specialized for the purpose of that tissue. For example, mitochondria contained in the liver are designed to convert ammonia into a less toxic waste substance known as urea in a series of reactions (7). Analysis of the breast muscle of chickens compared to the actively flying pigeon observed that the pigeon actually had a higher concentration of mitochondria in the breast muscle (8).
Both examples represent the differentiation of mitochondria and signify how both genetic and environmental factors influence mitochondria function.
Physiological Effects of the Mitochondria:
- Regulating ion concentrations such as calcium buffering critical to intracellular communication
- Maintain roles in fluctuating lipid levels
- Synthesizing products necessary for the transportation of glucose and insulin
- Providing sufficient energy for blood flow to and within the heart
- Regulating the removal of cellular damage or apoptosis if condition is deleterious enough to the mitochondrion’s function
Mitochondria Dysfunction and Health:
Now that research has enlightened our concept of how the mitochondria are more than just energy generators, the medical community now has a new field of research to investigate how mitochondria functional defects adversely affect human health. Currently, mitochondrial dysfunction is characteristic by a variety of metabolic illnesses and is not categorized as a disease (9).
Known as a neuroimmune disease, patients with multiple sclerosis frequently have impaired ATP synthesis. The lack of ATP is evidence of malfunctioning mitochondria. Also evident in most patients with multiple sclerosis is chronic oxidative stress.
Oxidative stress leads to severe health complications by producing excessive free radicals with a goal to complete demolition work to the structure of cells and inhibit their function. Mitochondria are primary targets of oxidative damage because they are the main sites of cellular respiration which free radicals may be generated in high amounts.( 9)
Reactive oxygen species (ROS) is an example of a powerful type of free radical that is also a necessary evil. ROS is an important key player in the function of cells but excessive amounts deplete beneficial antioxidants such as vitamin C and create destructive changes to the structure of the mitochondrion. The systemic or whole body inflammation seen in multiple sclerosis is believed to largely result from oxidative stress from excess pro-oxidants known as free radicals. (9)
Free radical production and damage is not the only factor to blame in illnesses associated with mitochondria dysfunction. A major implication in the pathogenesis of autism is the transfer of inflammatory signals across the blood brain barrier (9).
Inflammation of the central nervous system can be activated by an autoimmune response. As a consequence, specific biomarkers have been noted to “leak” away from the central nervous system causing disruption to both the brain and gastrointestinal tract. These inflammatory signals deplete the antioxidant levels associated with healthy function of mitochondria in the brain and intestines.
Like a game of Pacman, if the antioxidants are spending their time trying to neutralize the compounds causing inflammation that are typically not present, they are not fulfilling their originally designed purpose within the mitochondria. For example, carnitine is an essential amino acid required for producing ATP in the mitochondria. Individuals with autism have been consistently found to have reduced levels of carnitine. (9)
Abnormal Glutathione Pathways
Glutathione is another powerful antioxidant present in abundance in the brain. The brains of autistic children have been found to contain abnormal glutathione producing pathways and reduced glutathione concentrations.
Known as a depressive illness, bipolar disorder affects an individual’s mood and behavior. Symptoms of bipolar disorder include an extreme feeling of happiness or sadness, irritability, difficulty sleeping and the inability to maintain attention (10).
Unfortunately, individuals with bipolar disorder are at a higher risk of other illnesses such as ulcerative colitis. Although the development of the illness is still highly scrutinized, researchers have detected high levels of oxidative stress in these patients. Like adding lighter fluid to a flame, the oxidative stress present exacerbates any health complications present and creates new problems.
An increase in both reactive oxygen species and similar nitrogen species are often present in cases of chronic oxidative stress. With an increased presence of our body’s enemies, the human body fights back using its own defense system of antioxidants. Just as glutathione levels are found depleted in autistic individuals, patients battling other illnesses linked to mitochondria dysfunction including depression and Parkinson’s disease are influenced by significantly low levels of glutathione and thioredoxin systems (9).
Not only is glutathione a powerful antioxidant but the thioredoxin system is a defense system which aids in the removal of both reactive oxygen species and nitrogen species (2). Combined with glutathione, the two system’s combined efforts are highly efficient at limiting free radical damage and oxidative stress. It is as if Muhammad Ali and Mike Tyson have teamed up to defeat two mob leaders in a boxing match.
Chronic Fatigue and Fibromyalgia:
Patients with chronic fatigue syndrome (CFS) and fibromyalgia have visibly detectable changes in the structure of the mitochondria. Remember, the mitochondria are composed of different proteins and lipids which contribute to the membranes by which it is made up (1). The structures of these membranes are highly significant because they help maintain the life cycle of the mitochondria when it grows, splits or combines with another mitochondria.
Also apparent along one of the membranes in the mitochondria is the electron transport chain. As you now know, the electron transport chain is responsible for oxidative phosphorylation which is the process that creates ATP. Seen in CFS and fibromyalgia, the abnormal mitochondria structure results in a decrease in ATP synthesis (9).
Unfortunately, the perplexity of mitochondria dysfunction and type-2 diabetes puzzles the medical community. Questions have been raised whether mitochondria dysfunction may often times be the cause of type-2 diabetes. At the very least, the physiology of those patients with the condition exacerbates the effects of mitochondria dysfunction (7, 8).
Metformin, a commonly prescribed drug to treat diabetes, is actually known to induce mitochondria dysfunction and trigger problems that give rise to the development of diabetes (1). Basically, if you are taking metformin then you have been prescribed a medicine that is purposefully created to keep your body in a diabetic condition.
Associated with almost every known health problem, cancer is also correlated with mitochondria dysfunction. A site of high rates of respiration, tumor growth increases. Also as a result of the high rate of respiration, there is an increased risk of producing free radicals which can react with and harm the mitochondria’s own DNA.
As a result, common mitochondrial DNA mutations that occur increase the development of lung cancer, breast cancer and renal cell carcinoma. (1)
Heart failure has also been linked to mitochondria dysfunction. As we all know, the heart requires a constant supply of energy in the form of ATP to perform efficiently. Associated with mitochondria related myopathy, the heart is a critical organ that is affected by muscle weakness from defected mitochondria.
How To Maintain Mighty Mitochondria
Improving the function of your mitochondria can be as simple as making lifestyle changes. Certain strategies have been shown to treat symptoms associated with defected mitochondria. You can use these techniques beginning today to help you maintain mighty mitochondria.
Exercise can strengthen the performance of mitochondria in all areas of the body. Not only can exercise reduce oxidative stress when utilized appropriately, but exercise can increase mitochondrial activity by improving oxygen flow and blood pH (1).
As was evident in the comparison of the breast muscle of pigeons compared to chickens, individuals who run frequently have also been found to have a higher amount of functioning mitochondria than those who live sedentary lifestyles. (6, 8)
Intermittent Fasting and Mitochondria
When the body fasts, malfunctioning mitochondria can become what is called “purged” in a process known as autophagy or specifically, mitophagy (1, 3). Autophagy is a highly important capability for mitochondria to maintain because this ability enables the mitochondria to remove unwanted and damaged debris, accumulated both reactive oxygen and nitrogen species as well as unfolded proteins which no longer serve a purpose and can create virus like problems.
Ketogenic Diet to Fuel Your Mitochondria
A ketogenic diet which is rich in fat and low in carbohydrates has been used to suppress symptoms of muscle weakness and abnormal organ function associated with mitochondria dysfunction. The purpose of consuming a ketogenic diet is to change the metabolic state by which a body utilizes a specific food source for energy.
Ketones are alternative energy compounds which fuel cells when limited carbohydrates are available. Whereas carbohydrates use the electron transport chain within healthy mitochondria for energy production, fats are broken down by an entirely different process known as the TCA cycle (1). You may have just received a knot in your stomach if you remember the complexity of this process from your biology class.
The TCA cycle is an efficient energy pathway that the body can use to circumvent defected mitochondria. So effective, a ketogenic diet has been used to treat epilepsy which is a symptom of abnormal mitochondria in the hippocampus region of the brain. A ketogenic diet may also have therapeutic potential in alleviating symptoms associated with mitochondrial myopathy which prevents with a variety of symptoms of which all individuals have muscle weakness. (1)
The health of our mitochondria depends on our daily diets and the nutrients which we feed these small health promoting powerhouses. The structure by which mitochondria are designed to successfully create ATP is highly reliant on various types of structural proteins, enzymes and other key vitamins which can be supplemented with your diet. The following nutrients have been shown to treat mitochondria dysfunction: (1, 4, 6, 9)
Acetyl-carnitine: Acetyl-carnitine is produced by the body but can also be found in red meat. This amino acid is involved in transporting compounds and also stimulates glutathione production.
B Vitamins: Various B vitamins have been shown to play a critical role in mitochondria function such as biotin and vitamin B-12. B vitamins are highly specialized antioxidants and increase the synthesis of other strong antioxidants such as glutathione.
Alpha-Lipoic Acid: Alpha-lipoic acid has been especially shown to improve mitochondrial dysfunction in the brain and can improve cognitive ability.
Coenzyme Q10: Coenzyme Q10 (CoQ) is not only an antioxidant but it is also an essential component to the electron transport chain within the mitochondria. In other words, without CoQ10, there is no synthesis of ATP and therefore a defected mitochondrion. Oxidative stress can cause the mitochondrion to overconsume any available antioxidants and lead to a deficiency. Depending on the severity of symptoms, CoQ supplementation has been shown in studies to help with symptoms associated to CoQ deficiency.
Mitochondrial biogenesis is the process by which new mitochondria are formed. Researchers have only scraped the surface at understanding the series of cell signals that must occur in order for a mitochondria to either split into two known as fission or form a larger mitochondria when two combine contents in the process of fusion. What is understood is that several environmental influences control the rate and ability at which mitochondria grow and divide including: (8)
- Oxidative Stress
- Caloric restriction
The failure of mitochondrial biogenesis to occur has been implicated as a leading factor for many metabolic problems including myopathy, diabetes, Alzheimer’s disease as well as age related complications (1, 8). If the medical community is able to control the signals that enable mitochondria to grow and divide, they might also be able to control the severity of symptoms associated with mitochondrial dysfunction.
Human clinical trials remain to be conducted but successful treatment of animals utilizing a strategy of mitochondrial biogenesis to treat metabolic conditions shows positive results and may serve as a possible therapy to treating mitochondria dysfunction in the future.
If you learn only one thing about your health and mitochondria dysfunction, learn this. Oxidative stress can impair the function of mitochondria. Exposing your body to environmental contaminants in food, water, air, personal care products and depriving your body of essential nutrients are lifestyle risk factors that you can limit.
Feeding oxidative stress promotes further damage to mitochondria which in turn exacerbates illness and cancer. Left untreated, different illnesses and cancers will continue to cause oxidative stress and therefore completes a vicious cycle of deteriorating health.
Don’t fall prey to such a health consuming cycle. Promote a healthier future by reducing your risk of mitochondria dysfunction and master the health and performance of your mitochondria now.
Sources For This Article Include:
- McInnes J. Mitochondrial-associated metabolic disorders: foundations, pathologies and recent progress. Nutrition & Metabolism. 2013 Oct;10:63. DOI: 1186/1743-7075-10-63
- Ding WX, and Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012 Jul;393(7):547-564. PMCID: 3630798
- Liu J. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Neurochem Res. 2008 Jan;33(1):194-203. PMID: 17605107
- Gonzalez MJ, et al. The bio-energetic theory of carcinogenesis. Med Hypotheses. 2012 Oct;79(4):433-9. PMID: 22809841
- Massachusetts CFIDS/ME & FM Association: Mitochondrial Dysfunction. Link Here
- United Mitochondrial Disease Foundation Link Here
- Jornayvaz FR, and Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem. 2014 Jan; 47. PMCID: 3883043
- Morris G, and Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med. 2015 Apr;13:68. PMCID: 4382850
- National Institute of Mental Health: Bipolar Disorder. Link Here
Other Sources For This Article Include: