Mitochondria: Masters of Your Metabolism
Health is microscopic. Though too small to see with the naked eye, the cells that make up the systems of our bodies follow the arc of life: they’re born, grow and mature, learn and carry out functions, age, decline, and die.
Good cellular health manifests as robust energy, resilient immunity, a steady metabolism, and stable circadian rhythms. Cellular sickness, on the other hand, may manifest in a number of ways, ranging from weakness to inflammation to abnormal growth and reproduction. Inflamed or sick cells may cause damage to other cells, or in the case of cancer, cause overgrowth or blockages that impair normal function. Most cancer cells weren’t born that way – rather, these cells are sick and unable to recover. Is recovery even possible? Can a sick or senescent (declining) cell be healed? What role might nutrition and lifestyle play in this cellular process?
These questions are being investigated in the world of progressive cancer research, where a quiet revolution is taking place. Behind the scenes, independent thinkers are peeling back layers of the onion and finding the answer just might be yes, cancer cells can heal. These brave individuals have untethered themselves from the hands that feed them: the giants of the profit-driven drug industry. Free to investigate rather than contrive the results of their research, these archeologists of modern metabolic dysfunction have unearthed novel insights into what makes cellular health go awry. A whole new paradigm of abnormal cell growth has been emerging over recent years: that of mitochondrial dysfunction. These precious findings are still being dusted off, but for the nutritionally savvy, its key concepts may be applied now.
Let’s start with a basic understanding of what’s happening inside your cells.
What Are Mitochondria?
Mitochondria (singular: mitochondrion) are the tiny organelles that energize each cell, all tissues, and every organ in animals, plants, and fungi. In all cases, they catabolize (break down) glucose produced by plants to produce energy. Depending on energy demand, human cells contain anywhere from a few hundred mitochondria in skin cells to a few thousand in organs with high energy turnover, such as brain and liver cells; and tens of thousands in cardiac and skeletal muscle cells. Egg cells (oocytes) contain the highest number – as many as half a million mitochondria per egg – while sperm cells contain just 50-75, and only in the flagella, to power movement.
In terms of evolution, mitochondria are what enabled complex organisms to arise, including all plants, fungi, and animals. Mitochondria were formed when eukaryotes (nucleus-containing cells) engulfed bacteria, and rather than destroying them, formed a mutually beneficial relationship – a process known as endosymbiosis. Though we tend to think of bacteria as enemies, they are responsible for making life as we know it possible – and in our microbiomes, they continue to play a crucial role in human and animal life – including protecting our mitochondria.
Curiously, mitochondria contain their own DNA, which synthesize specific proteins within their inner membranes for the purpose of energy production. Mitochondria DNA is inherited exclusively from your mother (male sperm cell DNA is destroyed after the egg is fertilized). Mitochondrial DNA is therefore used to trace maternal lineages in genetic tests.
Mitochondria are the microscopic masters of your metabolism, powering everything from your beating heart to your blinking eyes to the neural networks that form your thoughts and enable you to read this article. Mitochondrial dysfunction therefore tends to show up in chronic and/or systemic conditions of energy deficiency, such as chronic fatigue, long Covid, brain fog, thyroid issues, fibromyalgia, congestive heart failure, Parkinson’s disease, dementia, Reynaud’s syndrome, multiple sclerosis, and of course cancer. Even loss of hair color as we age may be attributed to declining mitochondria in melanocytes (pigment-producing cells in hair follicles).1
Such conditions may be thought of as both a manifestation of and an underlying cause of mitochondrial dysfunction — that is, both a failure of cellular energy and a driver of further damage as a result. Together with chronic inflammation, loss of mitochondrial function may be considered one of the major driving forces of aging itself.
The Magic in the Matrix
Illustrations and microscopic images of mitochondria resemble something like a cross between a peanut and a caterpillar – funny oval objects with folded structures inside known as cristae. I’ve seen them represented in so many colors, they begin to resemble the contents of a piñata – and indeed, if you imagine breaking a cell open, thousands of mitochondria would spill out, though they wouldn’t be quite as colorful as those in the illustration above.
Inside these tiny organelles, the food you eat and the air you breathe are magically converted into energy, a process known as the Kreb cycle, the citric acid cycle, the tricarboxylic acid cycle (TCA), the mitochondrial matrix cycle, or simply cellular respiration. The word matrix has numerous definitions, depending on the context in which it’s used, but its most archaic meaning is simply “womb” – where animal life is formed. Mitochondria are like cellular wombs, keeping your body alive as glucose and oxygen enter their inner matrix – the holy of holies where the energy of life is created. There, a complex process of biochemical transformation creates adenosine triphosphate (ATP), the usable form of energy derived from adenosine (a sub-unit of DNA and RNA) and phosphorus, which indirectly captures the light of the sun (phosphorescent = light-bearing). Photosynthesis in plants captures sunlight to form glucose; cellular respiration releases and harnesses it for energy. In normal cellular respiration, this process is known as oxidative phosphorylation, or “OXPHOS,” which efficiently produces 28-32 molecules of ATP per molecule of glucose (figures vary). This is the ideal method of energy production that keeps your metabolism humming at an efficient rate.
Mitochondria are sensitive, however, and may easily be damaged by dietary and environmental toxins. If you’ve been reading this newsletter, these substances may already be familiar to you as drivers of inflammation and chronic diseases such as cancer, diabetes, neurodegenerative disorders, and aging itself. Damage to mitochondria may be precisely where, and how, these problems begin. Examples of mitotoxins include: alcohol; high fructose corn syrup; trans fats in processed meat; artificial sweeteners; preservatives such as BHA, sodium benzoate, and potassium bromate (used in bread flour); flavor enhancers such as MSG; heavy metals such as cadmium, mercury, arsenic, and lead; plastics such as BPA; pesticides; air pollution; advanced glycation end products (found in foods that are fried, broiled, grilled, smoked, roasted, or otherwise cooked at high temperatures); pharmaceutical drugs such as NSAIDs (especially Tylenol), antibiotics, Metformin (for diabetes), chemotherapy drugs; and above all, statins. Any drug that blocks, inhibits, or represses biochemical pathways (that is, most drugs) may work by impairing mitochondrial function. Over time, these substances sabotage your cells’ ability to properly metabolize glucose and produce energy, leading to insulin resistance, inflammation, and more mitochondrial dysfunction. Chronic stress also has a negative impact on your delicate organelles. High levels of insulin and chronically elevated cortisol repress the activity of mitochondria, reducing cellular energy and causing weight gain.2
“There has been a rapid increase in reports of the toxic effects of drugs and pollutants on the mitochondria in recent decades, interestingly correlating with an increase in insulin resistance prevalence.” 3
A more extensive list of drugs that may impact mitochondria may be found here.
Weak, abnormal, or dying cells may revert to alternative methods of energy production, such as glycolysis, which takes place in the cytoplasm of cells rather than inside the mitochondria. Glycolysis requires more glucose to produce far less energy – just two ATP molecules per molecule of glucose. This is one of the hallmarks of cancer, and explains why cancer cells consume so much sugar (and why very low carb/ketogenic diets may starve cancer). Cancer cells are tricky, however, and may resist drug treatments by switching from OXPHOS to glycolysis and back again.
Like people, some cells suffer a long decline before they die, costing the body a great deal as they can no longer function normally or perform their duties. Worse, these senescent or “zombie” cells are like vampires – living dead that suck energy from other cells. They may degrade into free radicals, causing oxidative stress and inflammation in any tissue or organ, and generating more free radicals in the process. This unfortunate snowballing effect begins in the mitochondria. How may we eliminate these rogue cells, or restore them to good health?
“Cancer cells aren’t alien invaders — They’re your own cells running the wrong program. And a drug that could repair that program — slow the engine down, reconnect some of the brakes — would be completely invisible in the standard drug test, because the cells don’t die. Killing the car — running it into a wall — is one way to stop the problem. But what if you could just fix the engine, unlock the steering, and reconnect the brakes? You would have a working car again.”
– Dr. Joseph Mercola4
While normal genetically-programmed cell death is known as apoptosis, mitophagy is the term for mitochondria that die prematurely due to damage or dysfunction. Mitophagy is triggered by toxins, oxidative stress, or loss of membrane potential. It’s a specialized form of autophagy, and it’s the cell’s effort to protect itself by eliminating bad mitochondria which may do more serious, long-term damage. This protective mechanism is a response to diminishing cellular function, and has therefore been linked to several aging-related conditions, including Parkinson’s disease, Lewy body dementia, sarcopenia (muscle wasting), and poor immune function.
From Harm to Healing
“Mitochondria, the body’s primary energy generators, and mitophagy, their quality control process, play key roles in maintaining immune balance. When mitophagy falters, immune cells lean toward exhaustion and inflammation. Scientists have hypothesized that safe, food-derived molecules that improve mitochondrial quality could strengthen immunity and enhance vaccine effectiveness.”5
Mitochondrial death is also the process by which many poisons work – for example, toxic mushrooms such as amanitas directly shut down mitochondrial function, as does cyanide poison. By contrast, medicinal mushrooms such as Reishi, Cordyceps, and Lions Mane may boost mitochondrial efficiency and ATP synthesis, and protect mitochondria from oxidative stress. More on this below.
Research shows promise for returning malfunctioning mitochondria to normal cellular respiration. According to independent cancer researcher Dr. Thomas Seyfried, mitochondrial dysfunction is “a credible alternative explanation for the origin of disease . . . . that cancer originates from damage to the mitochondria in the cytoplasm rather than from damage to the genome in the nucleus. The genomic damage in tumor cells follows, rather than precedes, disturbances in cellular respiration.”6
Regular exercise is by far the most powerful and effective strategy for supporting and healing mitochondria – endurance training, strength/resistance training, and high intensity intermittent aerobic exercise. Mitochondria want to be used; idleness does them no favor. Mitochondrial abundance and efficiency are regulated by several biochemical pathways, all of which are enhanced by strenuous exercise. Moderate or mild exercise has little effect. In muscle tissue, exercise increases fat oxidation, improves insulin sensitivity, and boosts mitochondrial number. In brain cells, aerobic exercise supports mitochondrial function by stimulating brain-derived neurotrophic factor (BDNF). Endurance training also increases mitochondrial density by as much as 50 to 100%.7
I’ve experimented with this approach by stimulating my brain while engaged in high-intensity exercise. I frequently do biochemical research on my phone while running on an elliptical treadmill. Pushing myself to keep apace with upbeat, rhythmic music, I simultaneously read scientific studies, look up new terms and concepts, and distill ideas for writing these articles. Breathing hard and sweating seems to light up my brain, enabling me to absorb information and synthesize ideas with greater ease. Clearly, increasing circulation and energy turnover in neural mitochondria enhances mental efficiency. My outlook on the hardships of life also improves after a hard workout, and my mind feels more relaxed. This feeling is so rewarding, it motivates me to do it again.
Other examples of stimulating the brain while engaged in high intensity exercise include choreographed dancing and tennis.
“Speaking generally, all parts of the body which have function, if used in moderation and exercised in labors, to which each is accustomed, become healthy and well-developed and age slowly. But if unused and left idle, they become liable to disease, defective in growth, and age quickly.” – Hippocrates, 4th century BCE
Various forms of temporary, positive stress known as hormesis also support healthy mitochondria. Examples include saunas, sweat lodges, ice baths, cold plunges, exposure to cold in winter, high-intensity intermittent training, and intermittent fasting. Fasting and caloric restriction also benefit mitochondria, as does proper hormonal balance. Estrogen, testosterone, thyroid hormones, cortisol, and insulin all affect mitochondrial abundance and efficiency, making hormonal balance a key factor in metabolic health.
An Unexpected Ally
Several key nutrients may also protect and restore mitochondria. About ten years ago, scientists discovered a curious molecule known as urolithin-A, a metabolite produced by healthy gut bacteria from ellagic acid, derived from foods containing ellagitannins. Of all foods on earth, pomegranates are the highest in ellagitannins – just one of many beneficial compounds found in this ancient Biblical fruit (see my article In Praise of Pomegranates for more on this subject). These amazing polyphenols may also be found in smaller amounts in walnuts, raspberries, and strawberries.
Only some people’s gut microbiomes can perform the conversion of ellagic acid to urolithin-A. Bacterial strains capable of producing urolithin-A belong mainly to the Gordonibacter/Ellagibacter group. These friendly microbes are not available as supplements, but may colonize a healthy gut in response to eating the right foods. Ellagitannin-rich foods also contain other beneficial polyphenols (and walnuts also contain healthy essential fats), so they are worth including in your diet. Pomegranate extracts are also effective. Ellagitannins have shown anti-tumor effects (particularly for prostate cancer), antioxidant and anti-inflammatory effects, and protection against neurodegenerative diseases – all through their action on mitochondria. They enhance mitophagy by tagging damaged mitochondria and activating your cellular garbage collectors, known as lysosomes. Urolithin-A also activates energy-sensing pathways known as AMPK; inhibits mTOR, a marker of unhealthy cellular growth; and reprograms immune cells such as NK and T-cells. This remarkable compound may even shift unhealthy cellular energy production away from glucose dependence and back toward healthy OXPHOS, enhancing overall metabolic efficiency and resilience.8 Urolithin-a is even known to attenuate the cardiotoxic effects of certain chemotherapy drugs.9
The ability to produce urolithin-A tends to decrease with age, even when the same ellagitannins are consumed. This is primarily due to loss of microbial diversity due to a lifetime of damage to gut bacteria from antibiotics and alcohol; as well as lower stomach acid, slower intestinal transit, and reduced intake or absorption of plant polyphenols. It is essential, therefore, to maintain a healthy gut microbiome, and to replenish your gut bacteria after exposure to antibiotics or alcohol with fermented foods, diverse forms of prebiotic fiber, and if necessary, probiotic supplements.
Supplements that directly supply urolithin-A are beginning to appear on the market; as of this writing, Timeline’s Mitopure is the only one I know of (and I cannot vouch for this product). Other bacterial strains, however, may help support the production of urolithin-A, such as Lactobacillus plantarum, Bifidobacterium pseudocantenulatam, and Akkermansia muciniphila, all of which may be found in certain fermented foods and/or supplements. Roughly 30-40% of the population is known to produce urolithin-A in their gut microbiome. This can be determined by a urine metabolite test after eating ellagitannin-rich foods.
Other Mitochondrial Nutrients
Coenzyme Q10 (a/k/a Ubiquinone), found in fatty fish and organ meats, acts as a “shuttle” for electrons within the mitochondria – a crucial part of cellular respiration. Statins directly block the production of CoQ10, which explains their common side effects of fatigue and loss of muscle strength. Mushrooms that contain natural, mild statins, such as Oysters and Shiitakes, do not.
Magnesium is an essential cofactor for ATP stability (as well as over 400 other biochemical functions). See my article Magnesium on My Mind to learn about the different roles and forms of magnesium.
NAD - (nicotinamide adenine dinucleotide) plays a crucial role in the citric acid cycle, supports mitochondrial biogenesis, activates fat metabolism, initiates cellular repair, and regulates “clock genes” in the brain that govern circadian rhythms and sleep. Your body makes NAD endogenously from foods rich in niacin (vitamin B3), tryptophan (amino acid), and certain key enzymes. NAD must not only be sufficient, but must cycle between an oxidized and a reduced form in order to maintain stability. Too much fluctuation may result in insomnia or feeling “tired and wired” during the day. Due to these factors, research on NAD supplements (or its precursors NMN and NR) shows mixed results at best.
The amino acid L-carnitine, found in grass-fed meat and wild-caught fish, acts as a transporter of fatty acids within the mitochondria.
Omega-3 essential fatty acids, derived from liver and small fatty fish, strengthen and repair delicate mitochondrial membranes. This is critical for mitochondrial health!
Creatine is known for its ergogenic effects – that is, it enhances physical performance, stamina, and recovery, and increases muscle mass and efficiency (only with regular strength training). Less known is creatine’s ability to maintain mitochondrial ATP production and increase mitochondrial density in the brain. It also has a stabilizing effect on metabolically active brain tissue under pathological or high-demand conditions, such as traumatic brain injury, sleep deprivation, or cognitive overload. This may be precisely how creatine helps prevent cognitive decline. Creatine is found in red meat, fish, and poultry. High heat cooking may destroy it. Plant-based foods do not contain creatine. Older adults may need to supplement. It’s essential to drink plenty of water with creatine supplements in order to protect the kidneys. Periodic testing of kidney enzymes with creatine supplementation is recommended.10
“Creatine-deficient syndromes involving brain creatine depletion are characterized by major mental and developmental disorders (e.g., mental retardation, learning delays, autism, and seizures) . . . . Cognitive processing may also be affected by creatine metabolism, as it may facilitate ATP homeostasis during periods of rapid or altered brain ATP turnover, such as during complex cognitive tasks, hypoxia, sleep deprivation, and some neurological conditions.” 11
Certain medicinal herbs and nutrients are also known to support, protect, and enhance mitochondrial function, often by improving ATP production, reducing oxidative stress, or boosting mitochondrial biogenesis. Key examples include Cordyceps mushrooms, Ashwagandha, ginseng, curcumin extract (from turmeric root), Eleuthero (Siberian Ginseng), and green tea12 (see my article Your Adaptogenic Allies for more on this subject). High quality extracts of Maitake mushroom contain cytoprotective D-fractions that increase mitochondrial density, lower inflammation, and improve metabolic signaling pathways throughout the body, thereby correlating with lower cardiovascular risk and lower risk of cancer.13
Mushrooms are also the richest dietary source of ergothioneine, a sulfur-containing amino acid that behaves as a targeted cellular protectant. Once absorbed, ergothioneine concentrates in tissues with high oxidative stress, high mitochondrial activity (energy turnover), and high damage risk – especially neurons, the lens of the eye, liver hepatocytes, and certain blood cells. Ergothioneines act as a mitochondrial shield, a heavy-metal chelator, and a persistent antioxidant that is not quickly depleted.
Mitochondria in Medicine
Functional and holistic practitioners are already offering a variety of tests and ways to support mitochondrial recovery and health. In the coming months and years, we’ll be seeing more and more products on the market that speak to this need. At this writing, accessible and reliable lab tests include:
Lactate ± pyruvate – to determine pyruvate metabolism, part of the cellular respiratory chain. High lactic acid indicates oxygen shortage and mitochondrial dysfunction, especially in neurological disorders.
Organic acid test (OAT) – to measure various metabolites formed in the process of energy production.
VO₂ max – a marker of cellular oxygen-burning efficiency, considered the “gold standard” test for metabolic capacity and longevity. (See footnote for how to do this yourself.)14
Muscle biopsies (an invasive procedure used only for specific diagnostic purposes).
Most people can feel how well their cells are producing energy without any lab tests. But once we understand the underlying role of our mitochondria, we may begin to see conditions previously believed to be genetic, random, inevitable, or just plain unlucky in a new light: as a manifestation of mitochondrial function. All chronic conditions, whether positive or negative, arise from your mitochondria; and the unseen arc of their lives underlies your own path of aging. Life runs on energy, and maintaining a steady flow is the key to vitality, immunity, mobility, and cognition.
Beyond boosting the trillions of microscopic energy factories that power your metabolism, my hope is that this article has inspired you to think about your health on a cellular level. How ironic that the tiniest substructures of our bodies hold so much power! If we can begin to think of conditions like cancer and Alzheimers disease as impeded cellular energy rather than invading enemies, perhaps we can begin to support, rather than attack, errant cells. Anything you do to nourish and heal these amazing life-sustaining organelles will benefit your entire health.
It takes time to renew your mitochondria. It’s like repairing and retuning the instruments of an entire symphony orchestra. One by one, the strings and reeds, flutes and horns come into harmony. The effects of mitochondrial rejuvenation may surprise you, and feed your motivation to make further improvements to your health.
We are walking biochemical energy systems. If we want our cells to grow, function, and reproduce normally, we need to take care of them, feed them properly, and protect them from harm. The more we hold precious the health of our cells, the better they can serve us. The happier your mitochondria, the more abundant your energy. The more abundant your energy, the happier are you.
This Mother’s Day, I’ll be thanking my mom for passing her mitochondria to me. She’s turning 90 next week. Good job, Mom. We have my maternal grandmother and great-grandmother to thank, too. Their good energy continues to trickle down the generations to my own children, and perhaps someday my grandchildren and great-grandchildren, and beyond.
To your good health –
Yael Bernhard
Certified Integrative Health & Nutrition Coach
Yael Bernhard is a writer, illustrator, book designer and fine art painter with a lifelong passion for nutrition and herbal medicine. She was certified by Duke University as an Integrative Health Coach in 2021 and by Cornell University in Nutrition & Healthy Living in 2022. For information about private health coaching or nutrition programs for schools, please respond directly to this newsletter, or email dyaelbernhard@protonmail.com. Visit her online gallery of illustration, fine art, and children’s books here.
Information in this newsletter is provided for educational – and inspirational – purposes only.
Have you seen my other Substack, Image of the Week? Each week devotes a short post to one illustration or work of fine art, and shares the story and creative process behind it.
Mitochondrial dysfunction is often linked to the dose, duration, and patient-specific factors https://pmc.ncbi.nlm.nih.gov/articles/PMC6925523/
Kuretu A, Arineitwe C, Mothibe M, Ngubane P, Khathi A and Sibiya N (2023) Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments. Front. Endocrinol. 14:1123928. doi: 10.3389/fendo.2023.1123928
https://articles.mercola.com/sites/articles/archive/2026/04/13/aspirin-salicylate-cancer.aspx
https://www.news-medical.net/news/20251103/Urolithin-A-recharges-aging-immune-cells-and-boosts-mitochondrial-fitness-in-midlife-adults.aspx
https://pmc.ncbi.nlm.nih.gov/articles/PMC4493566/
https://www.sciencedirect.com/science/article/pii/S0021925818960461
https://scispace.com/papers/the-role-of-exercise-and-pgc1a-in-inflammation-and-chronic-2xqbwtaowh
https://pubmed.ncbi.nlm.nih.gov/23733637/
https://www.news-medical.net/news/20251103/Urolithin-A-recharges-aging-immune-cells-and-boosts-mitochondrial-fitness-in-midlife-adults.aspx
https://pmc.ncbi.nlm.nih.gov/articles/PMC10609777/
https://pmc.ncbi.nlm.nih.gov/articles/PMC8617978/
https://www.genesispub.org/resource/images/articles/pdf462.pdf
https://www.sciencedirect.com/science/article/pii/S2589004225000744
https://www.nature.com/articles/s43587-025-00996-x
https://www.sciencedirect.com/science/article/abs/pii/S000927972400509X
While the VO2 max test is normally done in a lab with wearable trackers, you can calculate your own score by using an elliptical treadmill that collects basic data. While running hard with maximum resistance, take note of your BPM (heartbeats per minute), RPM (speed of running), METs (a marker of metabolic output that many treadmills measure), and watts (a marker of energy output in relation to resistance level). Feed this data into AI together with your age, weight, and sex, and it will calculate and interpret your VO2 max. This method may not be as accurate as a lab test, but it’s a good start, and may serve as a useful baseline for future comparison.