What is Mitochondrial Dysfunction? Causes, Symptoms, and Treatment

Author : Ari Whitten
Medical Reviewer: Evan Hirsh, M.D.


What are Mitochondria?

Mitochondria are known as the powerhouses of energy factories of the body. They are vital to our survival as they generate energy in the form of ATP from the food we eat. This process is known as cellular respiration. 

Mitochondria produce more than 90% of the energy needed by the body to sustain life and support organ function. 1 Loss of function in mitochondria results in excess fatigue and other symptoms that are common complaints in almost every chronic disease, ranging from Alzheimer’s and cardiovascular disease to diabetes and autism. 2 Mitochondria are the crux of health, energy, and longevity. 3

Although energy production is a vitally important function, to say that mitochondria only produce energy would be to underestimate their role vastly. Mitochondria are needed for making RNA and DNA, for the synthesis of hemoglobin, cholesterol, metabolism, estrogen and testosterone synthesis, neurotransmitter metabolism, and free radical production and detoxification. In addition, in the liver, mitochondria are specialized to detoxify ammonia in the urea cycle. 4

What are Mitochondrial Diseases?

A mutation causes mitochondrial disease or ‘mito’ for short in one or more of the genes that make up the mitochondria. These faulty genes can be inherited from the mother or the father. Research shows that mitochondrial mutations are present in at least 1 in 200 people and that around 1 in 5,000 will develop severe illness. Multiple organ systems can be involved with mitochondrial disease, and a wide range of symptoms are associated with it. 

Mitochondrial dysfunction occurs when the mitochondria do not work as well as they should due to another disease or condition. This is distinct from the mitochondrial disease in that it does not usually involve an inherited genetic component. 

When mitochondria are damaged, they produce less and less energy, which results in compromised cell function and even cell death. When this progresses further, it can result in system-wide damage and dysfunction. The parts of the body that use the most energy are generally most affected by mitochondrial disease and dysfunction. This includes the heart, brain, muscles, and lungs. 5

Causes of Mitochondrial Dysfunction

Mitochondrial dysfunction can result from an inadequate number of mitochondria, an inability to transport necessary metabolites into mitochondria, or dysfunction in cellular respiration, particularly in the electron transport chain. 6This may occur as a result of the adverse effects of drugs, infections, and other environmental toxins, a poor diet, or the body’s decreased capacity to handle stress (resilience).

Mitochondria are evolved to sense threats and act as danger sensors. One of the most ancient functions of mitochondria in cellular defense and when danger is detected, mitochondria alter cellular metabolism to help shield the cell from further injury.7This results in the stiffening of cell membranes and an increase in the production of reactive oxygen species (ROS), which precipitates a corollary downward shift in energy production.

When mitochondria shift from making energy into defense mode, that’s when dysfunction happens. Lower energy production and higher ROS production results in further damage to the mitochondria and a self-perpetuating downward spiral of fatigue. This, in turn, decreases mitochondrial resilience (or ability to deal with additional stress). 

Resistance to stress parallels the health of your mitochondria. The more mitochondria you have, the higher is your capacity to adapt and deal with stressors. Lack of mitochondrial stimulation is the key to its declining function. Mitochondria are stimulated by exposure to hormetic stressors. Hormetic stressors are mild and/or acute stressors that increase resistance to other stressors and thus increase the health, resilience, and vitality of the organism. Exercise is an excellent example of a hormetic stressor. The philosopher Friedrich Nietzsche said, “That which does not kill us makes us stronger,” he could have been describing this process of Hormesis. 

As discussed previously, mitochondrial disorders may also be caused by mutations (acquired or inherited), in mitochondrial DNA (mtDNA), or in nuclear genes that code for mitochondrial components. 

Nuclear DNA has two copies per cell, and one copy is inherited from the father and the other from the mother. Mitochondrial DNA, however, is exclusively inherited from the mother, and each mitochondrial organelle typically contains between 2 and 10 mtDNA copies. When cells divide, and genes are copied, mutations can be passed on or occur during replication.  

In autosomal recessive inheritance: This child receives one mutated copy of a gene from each parent. There is a 25% chance that each child in the family will inherit a mitochondrial disease.

In autosomal dominant inheritance: This child receives one mutated copy of a gene from either parent. There is a 50% chance that each child in the family will inherit a mitochondrial disease.

In mitochondrial inheritance: Mutations in the mitochondrial DNA are passed from mother to child. If this is the way a mitochondrial disease is inherited, there is a 100% chance that each child in the family will inherit a mitochondrial disease.

Random mutations: Sometimes, genes develop a mutation of their own that is not inherited from a parent.

Symptoms of Mitochondrial Dysfunction

Symptoms of mitochondrial diseases depending on which cells of the body are affected. As a rule, mitochondrial diseases are worse when the defective mitochondria are present in the muscles, cerebrum, or nerves,8because these cells use more energy than most other cells in the body. Symptoms can range from mild to severe, involve one or more organs, and can occur at any age. Even in people with the same mitochondrial disease, symptoms, severity, and age of onset (start of symptoms) may vary. 

The most common symptoms are fatigue 9 10 11. Brain fog is also common if the mitochondria in your brain are not working so well. 

Other symptoms include:

Most chronic diseases/conditions can also be linked to mitochondrial dysfunction. This includes:

  • Cardiovascular disease 20 21
  • Lung disease 22
  • Vision and hearing problems 23 24
  • Learning disabilities
  • Autism 25 26 27
  • Liver and kidney disease 28 29 
  • Gastrointestinal disorders 30
  • Diabetes 31 32 33
  • Neurological diseases (including dementia) 34 35 36
  • Movement disorders 37

Getting a Diagnosis

Mitochondria Pain

When the ability of the mitochondria to make ATP appropriately in response to energy demands is compromised, you have mitochondrial dysfunction. There are many methods to assess this dysfunction. 

A popular method among functional medicine practitioners is the Kalish method, made famous by Dr. Daniel Kalish. The Kalish Method is a functional medicine lab-based health approach focused on restoring the three main body systems: hormones, digestion, and detoxification. 38 As such, it employs three main tests, first a salivary cortisol test, second a stool test (to check the integrity of the gut), and lastly, an organic acids test. 

The final analysis is critical as it evaluates 46 metabolites from digestion, assimilation, metabolism, and the production of ATP. If one or more pathway is not functioning correctly, the organic acids will “overflow” into the urine. 39 This one test gives you a great overall snapshot of the health of your body systems. It also highlights problem areas for further testing. 

Other tests include biochemical tests on urine, blood and spinal fluid, a muscle biopsy to examine the mitochondria and test enzyme levels, and magnetic resonance imaging (MRI) of the brain and spine. Testing depends on symptoms and may include echocardiography, electrocardiography (EKG), eye examinations, and hearing tests. Diagnoses can be made through a combination of clinical observations, laboratory evaluations, and other tests. 

Links to Other Diseases

Loss of function in mitochondria, the key organelle responsible for cellular energy production, is a characteristic of aging and virtually all chronic diseases. 

These diseases include:

  • Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Friedreich’s ataxia 40 41 42 43
  • Cardiovascular diseases, such as atherosclerosis and other heart and vascular conditions 44 45
  • Diabetes and metabolic syndrome 46 47 48
  • Autoimmune diseases, such as multiple sclerosis and lupus 49 50 51
  • Neurobehavioral and psychiatric diseases, such as autism spectrum disorders, schizophrenia, and bipolar and mood disorders 52 53 54 55
  • Gastrointestinal disorders 56 57 ; fatiguing illnesses, such as chronic fatigue syndrome and Gulf War illnesses 58 59
  • Musculoskeletal diseases, such as fibromyalgia and skeletal muscle hypertrophy/atrophy 60 61
  • Cancer 62 63
  • Chronic infections 64 65


There are no cures for mitochondrial diseases, but treatment can help reduce symptoms or slow disease progression. Treatment varies by the specific mitochondrial disease diagnosed, its severity, the associated symptoms, the age of the patient, and from person to person. 

Treatments for mitochondrial disease may include:

Vitamins and supplements: 

Including Coenzyme Q10, B complex vitamins, especially thiamine (B1) and riboflavin (B2); magnesium, astaxanthin, alpha-lipoic acid, Acetyl-L-carnitine, creatine, D-ribose, taurine and turmeric among others. For more information, read “The Best Vitamins and Supplements to Fight Fatigue.”


Both endurance exercises and resistance/strength training. These are done to increase muscle size and strength and activate mitochondrial biogenesis (the process by which your body makes more mitochondria). For trained athletes, performing high-intensity interval training (HIIT) has been shown to improve mitochondrial function and energy levels dramatically. 66 67

A phytonutrient-rich diet: 

Certain plant phytonutrients act as pro-oxidants in the body, which activates the body’s antioxidant defense system. This includes but is not limited to polyphenols such as resveratrol from red grapes, sulforaphane from broccoli, curcumin from turmeric, ECGC from green tea, and carotenoids from tomatoes. The antioxidant defense system, once activated, in turn, activates detoxification pathways and stimulates mitochondrial biogenesis. 

Ketogenic diets and intermittent fasting: 

A ketogenic diet, which is high in fat, moderate in protein, and very low in carbohydrates, is often used in the treatment of mitochondrial dysfunction. It was first used to treat epilepsy by mimicking the effects of fasting. 68 It stimulates mitochondrial biogenesis and thereby reduces the energy deficiency that is the hallmark of mitochondrial dysfunction. 69 Similarly, intermittent fasting and caloric restriction are also effective treatments. They are all hormetic stressors that stimulate the mitochondria to become more resilient.

Other Hormetic Stressors: 

Cold exposure (such as cold showers), heat exposure (through sauna use), hypoxia, red and near infra-red light exposure, UV light exposure, and certain xenobiotics (such as caffeine and other drugs) work by producing temporary stress that stimulates mitochondrial adaptations, which improves resilience and dramatically increases energy levels.

Avoiding environmental toxins: 

Remove toxins from your body and your environment to improve your energy levels. 

Toxins directly contribute to fatigue by exhausting the body’s efforts to fight off the toxic invaders. Toxins in your environment include fluoride in toothpaste and tap water, BPA and phthalates in plastic, heavy metals in farmed fish, canned goods and cookware, food coloring, perfume, over-the-counter drugs, etc.

 It also includes the use of alcohol, cigarettes, and monosodium glutamate (MSG is a flavor enhancer commonly added to Chinese food, canned vegetables, soups, and processed meats) as well as certain prescription medications. In addition, environmental pollution may affect the health of your mitochondria and should be avoided and/or minimized. 70

Getting Adequate Sleep: 

Sleep is critical for recharging the body’s energy stores and for the process of autophagy (your body’s way of removing damaged cells and replacing them with new ones) to occur. This can be achieved by sleeping in a completely dark and cold room, 71 having a simple, regular, pre-bed ritual, which includes something relaxing and avoiding food for 3-4 hours before bed. Exposure to sunlight during the day, especially in the first 30 minutes after you wake up, is also crucial for the regulation of your sleep/wake cycle. 

Minimizing Psychological Stress: 

A few things cause tiredness and fatigue faster than intense psychological or emotional stress. Everyone experiences some stress, but it is when it is chronic that it becomes problematic. To manage stress, practice daily recharge rituals such as mindfulness, meditation, prayer, deep breathing, and laughter. 

Meditation is, by far, one of the most potent medicines available to humans. It decreases stress, anxiety, pain, inflammation, and depression, and improves mood, cognition, happiness, and a sense of connection to others. 72 73 74 75 76 Spending time in nature, practicing a hobby, living with purpose, and cultivating a community may also help alleviate stress. 

Supportive treatments: 

These include speech therapy, physical therapy, respiratory therapy, and occupational therapy.

How effective is the treatment?

Treatment of mitochondrial disease is still in its infancy. Aside from symptom-based management, treatment of mitochondrial disease focuses on maintaining optimal health, using measures to reduce symptom flare-ups during physiologic stress (such as infection, dehydration or surgery), and avoiding mitochondrial toxins. 77

Effectiveness varies from patient to patient, depending on the exact disorder and the severity of the disorder. As a general rule, those with mild disorders tend to respond to treatment better than those with severe disorders. It must be noted that most treatments cannot reverse physical damage that has already been sustained, such as brain malformations, but can be useful in delaying or stopping the progression of the disease. 

Treatment should always be tailored by the patient’s physician to meet that patient’s needs. This avoids unnecessary and possibly dangerous procedures. The benefits of a particular treatment protocol aren’t always immediately apparent and can sometimes take months to notice. A strong supportive community is essential for encouragement and compliance. 


Mitochondrial dysfunction occurs when mitochondria do not work effectively, resulting in less energy being produced, increased fragility, accelerated aging, and disease. The leading cause, other than genetics, is a lack of stimulation of mitochondria, which affects its size, number, and resilience. Symptoms vary from fatigue and neurological issues to muscle weakness and poor blood sugar control, depending on where the mitochondria are situated. 

As mitochondria are the powerhouses of the cell, when they dysfunction, whole systems can be affected. Treatment includes vitamins and supplements, exercise, a phytonutrient-rich diet, adequate sleep, stress reduction, avoiding toxins, a ketogenic diet, and intermittent fasting as well as other types of hormesis. The effectiveness of treatment varies by condition, severity, and from person to person. It is a good idea to work with a primary care physician and/or a team of healthcare practitioners to ascertain the best treatment for each individual.


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Medically Reviewed ByEvan Hirsh, M.D.

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