Without an engine, cars cannot convert fuel into the energy necessary to propel the car. Human cells have similar engines that convert food from the diet into the energy necessary to run the cells of the body, among other vital functions. These “powerhouses of the cell” are called mitochondria (1).
What are these amazing energy-producing engines? What is their relationship to energy, and what can cause their dysfunction? Join us for a 3-part series that focuses on these vital cellular structures.
Human cells typically have a nucleus that holds DNA and functions as the command center for the cell. The boundary of the cell is its outer membrane. Between the nucleus and the cell membrane is the cytoplasm, a gel-like substance that gives form to the cell and cushions many “organelles” within it. Organelles such as mitochondria are tiny structures that have a particular function or set of functions they provide for the cell. Mitochondria float in the cytoplasm of the cell, providing a stunning array of functions, such as creating the energy needed for the cell’s biochemical reactions.
Oddly, there is no set number of mitochondria per cell, but the numbers seem to correspond with the energy requirements. A single human cell could have hundreds or even thousands of mitochondria, all working to supply energy and perform their other functions. High energy users such as the liver, kidney, and muscles have high numbers of mitochondria. In heart muscle cells, about 40% of the cytoplasm is filled with mitochondria, because the heart’s energy needs are so high (1).
Functions of Mitochondria – Why are they so Important?
Mitochondria are middle-men of sorts, responding to signals from genes, metabolism, and hormone-producing nerve cells. Their responses change the structure or function of mitochondria, which in turn affects a vast array of structures and functions in the body. Indeed, mitochondria have been called a “portal” because they sit between the cell and its environment, being influenced by and influencing so many processes in the body (2). Here are just a few of the very important functions that mitochondria perform (1, 3):
1) Mitochondria make energy for cellular processes. One of the most important functions of mitochondria is to synthesize adenosine triphosphate (ATP). ATP is an organic chemical that is created by mitochondria from food molecules and oxygen in a series of chemical reactions, creating a portable form of energy a cell of the body can use as it needs it. When the cell needs energy, it can break the chemical bonds of the ATP and release its energy. Once the ATP is created, it leaves the mitochondria and floats around in the cytoplasm until it is utilized. Without ATP, the cell would not be able to synthesize proteins, move substances across the cell membrane, or grow or divide properly. Without ATP, the cell eventually dies.
2) Programmed cell death is controlled by mitochondria. Mitochondria can initiate and regulate programmed cell death, affecting cellular longevity. Cells get created, live for some amount of time, then die either spontaneously (and messily) or self-destruct in a controlled fashion (apoptosis). When certain criteria are fulfilled, mitochondria will start the sequence of actions that will cause the cell to self-destruct in a controlled manner, allowing it to be broken down and its materials recycled.
3) Mitochondria can store and release calcium. The ability of mitochondria to store and release calcium affects a variety of cells and functions. Calcium is very important to muscles, as it helps muscles to initiate and sustain contraction. Without calcium, we’d be unable to walk! Calcium also helps regulate the secretion of certain hormones and neurotransmitter substances (chemical messengers in the brain). Mitochondria can release calcium when stores are low, which can prevent stress on the cells.
4) Without mitochondria, the body would be unable to transport oxygen or have certain types of cell membranes. Mitochondria provide the co-factors and intermediate chemicals necessary to make cholesterol and heme molecules. Heme is the red element of the blood that carries oxygen. Without heme, we’d be unable to utilize oxygen in our bodies. Cholesterol is incorporated into many cell membranes in the body, providing strength and flexibility to the cell. Without cholesterol, some cell membranes would not form or would rupture easily, increasing the risk of infection and impairing the function of tissues and organs.
Mitochondria, Metabolism, and Energy
Metabolism is the set of chemical processes in the body that utilize food as energy, creating some byproducts that are considered waste. Metabolism’s limiting factor is the amount of energy available to it, so one of the body’s biggest balancing acts is making sure it gets enough energy without getting too much, which is known as homeostasis. If too little energy is derived from raw materials, metabolism slows and can be experienced as fatigue or lethargy. If too much raw material for energy is supplied and the body cannot use it all, it can lead to weight gain or metabolic conditions such as diabetes.
Since mitochondria produce ATP, one of the fundamental units of energy used in the body, mitochondria are able to affect just about every metabolic process in the human body – positively or negatively. The parts of the body that need energy the most (the brain, liver, kidneys, and muscles) suffer the most if the important work of mitochondria is disrupted. It is widely believed that disruption of mitochondria can negatively affect the functioning of the brain because brains require so much energy to run properly (4). Indeed, neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease are associated with mitochondrial dysfunction of one sort or another.
Mitochondrial Dysfunction and Mitochondrial Diseases
Properly functioning mitochondria are vital for human health. Yet, dysfunction should be distinguished from disease. In mitochondrial dysfunction, the mitochondria may be experiencing issues but still be able to produce a little energy. For more information and a list of symptoms associated with mitochondrial dysfunction, please see our previous article.
Mitochondrial disease is more severe, so greatly affecting functionality that no energy is produced at all. The cell will eventually die because of the inability to make ATP properly. Widespread cell death can lead to organ failure and other serious and life-threatening situations.
Causes of Primary and Secondary Mitochondrial Diseases
Primary mitochondrial disease is a genetic or biochemical condition that affects the functioning of mitochondria. Estimates indicate that 1 in 5,000 people have a genetic mitochondrial disease (5). Mitochondria have their own DNA, which is passed down through the mother’s line of genetics. Mutations in this mitochondrial DNA can lead to a wide array of conditions and symptoms. Unfortunately, these primary diseases typically worsen with time.
Below is a list of important bodily functions that can be negatively affected by primary mitochondrial disease (6):
Hearing, seeing, breathing, speaking, moving
Digestion and functions related to digestion (gut motility, liver function, pancreas function, and stool frequency)
Heart, liver, lung, and kidney function
Hormone imbalances: adrenal, thyroid, parathyroid, pancreas, and growth hormone
Secondary mitochondrial diseases are all conditions that cause mitochondrial damage but don’t have their origins in the mitochondria itself. For example, the origins could be an infection, a metabolic disorder (such as diabetes), or a medication. For example, it is thought that Parkinson’s disease can cause secondary mitochondrial disease (7) as well as Alzheimer’s, muscular dystrophy, Lou Gehrig’s disease, diabetes, and cancer (5). The results of secondary mitochondrial disease are similar in nature to those caused by primary mitochondrial disease. However, treatment options may differ. Treating the root cause should result in a reduction in mitochondrial damage.
Additional Causes of Mitochondrial Dysfunction
Science is catching up to the complexity that mitochondria represent. However, it is doubtful that all underlying mechanisms of mitochondrial dysfunction are known. Diet and lifestyle influences, as well as toxin or radiation exposure, can shift mitochondria from functioning well to a state of dysfunction.
1) Diet and lifestyle influences (epigenetics) – Exercise level and diet can cause changes in the expression of genetic material without changing the underlying genes. When the expression of genes is changed, it’s called “epigenetics,” meaning “above the genes.” Typically, this involves mechanisms that cause a different protein to be made, or fewer proteins to be made. In the case of mitochondria, epigenetics can change the expression of genes of mitochondrial DNA and change the expression of genes in the cell nucleus (8).
Why it matters: The significance of epigenetic changes influencing expression of DNA in the mitochondria and the cell nucleus, is that diet and exercise can be manipulated to have a favorable rather than negative epigenetic impact.
For example, an increase in exercise can cause an increase in the number of mitochondria in the cytoplasm, increasing ATP production. Additionally, environmental factors and diet can be altered to disrupt or enhance methylation, which is one of the ways the expression of genes can be changed.
2) Toxin or radiation exposure – Two factors that can feed into primary mitochondrial dysfunction are exposure to toxins (9) and radiation (10). Both of these may cause mutations in mitochondrial DNA or cause secondary conditions that can lead to mitochondrial dysfunction. Heavy metals are toxins that often find their way into our bodies, acting as neurotoxins or weakening the immune system.
Why it matters: Tests for toxins such as metals can be performed, quantifying the exposure. Measures can be taken to remove the toxins from the body, such as metal detoxification, with testing confirming the reduction. Measures can be taken to reduce radiation or to soften the impact on the body.
The well-being of mitochondria is extremely important to health. Learning how to positively influence mitochondria can improve human health, helping to prevent or alleviate unpleasant and often hard-to-diagnose symptoms. Now that the importance of mitochondrial health has been made clear along with some of the underlying mechanisms, the next two articles will be deep dives into various treatments for mitochondrial dysfunction. If you experience some of the symptoms listed in our earlier article, please make an appointment to see us. There is no single diagnostic test for mitochondrial disorders, but there are meaningful tests we can perform that, coupled with our knowledge and experience, can help us guide you to a healthier existence.
Jonathan Vellinga, MD is an Internal Medicine practitioner with a broad interest in medicine. He graduated Summa cum laude from Weber State University in Clinical Laboratory Sciences and completed his medical degree from the Medical College of Wisconsin.
Upon graduation from medical school, he completed his Internal Medicine residency at the University of Michigan. Dr. Vellinga is board-certified with the American Board of Internal Medicine and a member of the Institute for Functional Medicine.
1. Mitochondria: Form, function, and disease [Internet]. Medical News Today. MediLexicon International; [cited 2023Feb16]. Available from: https://www.medicalnewstoday.com/articles/320875
2. Picard M, Wallace DC, Burelle Y. The rise of mitochondria in medicine [Internet]. Mitochondrion. U.S. National Library of Medicine; 2016 [cited 2023Feb16]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023480/
3. BioExplorer. Top 6 mitochondria functions & roles: Biology explorer [Internet]. Bio Explorer. 2019 [cited 2023Feb16]. Available from: https://www.bioexplorer.net/mitochondria-functions.html/
4. Trigo D;Avelar C;Fernandes M;Sá J;da Cruz E Silva O; Mitochondria, energy, and metabolism in neuronal health and disease [Internet]. FEBS letters. U.S. National Library of Medicine; [cited 2023Feb16]. Available from: https://pubmed.ncbi.nlm.nih.gov/35088449/
5. Mitochondrial diseases: Causes, symptoms, diagnosis & treatment [Internet]. Cleveland Clinic. [cited 2023Feb16]. Available from: https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases
6. Parikh S, Goldstein A, Karaa A, Koenig M, Anselm I, Brunel-Guitton C, et al. [PDF] Patient Care Standards for primary mitochondrial disease: A consensus statement from the Mitochondrial Medicine Society: Semantic scholar [Internet]. Genetics in Medicine. 1970 [cited 2023Feb16]. Available from: https://www.semanticscholar.org/paper/Patient-care-standards-for-primary-mitochondrial-a-Parikh-Goldstein/aa1115c19f1c03480ef5e94ae8f102af926f412e
7. DS; K. Treatment of mitochondrial electron transport chain disorders: A review of clinical trials over the past decade [Internet]. Molecular genetics and metabolism. U.S. National Library of Medicine; [cited 2023Feb16]. Available from: https://pubmed.ncbi.nlm.nih.gov/20060349/
8. Manev H, Dzitoyeva S. Progress in mitochondrial epigenetics [Internet]. De Gruyter. De Gruyter; 2013 [cited 2023Feb16]. Available from: https://www.degruyter.com/document/doi/10.1515/bmc-2013-0005/html
9. Lim S. Persistent organic pollutants, mitochondrial dysfunction, and metabolic syndrome [Internet]. Annals of the New York Academy of Sciences. 2015 [cited 2023Feb16]. Available from: https://www.academia.edu/12202690/Persistent_organic_pollutants_mitochondrial_dysfunction_and_metabolic_syndrome?from=cover_page
10. Amorim NML;Kee A;Coster ACF;Lucas C;Bould S;Daniel S;Weir JM;Mellett NA;Barbour J;Meikle PJ;Cohn RJ;Turner N;Hardeman EC;Simar D; Irradiation impairs mitochondrial function and skeletal muscle oxidative capacity: Significance for metabolic complications in cancer survivors [Internet]. Metabolism: clinical and experimental. U.S. National Library of Medicine; [cited 2023Feb16]. Available from: https://pubmed.ncbi.nlm.nih.gov/31765667/