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If you've ever felt sluggish despite eating healthy foods, or wondered why exercise seems to help with so many different health conditions, the answer might lie in tiny structures inside your cells called mitochondria. A comprehensive 2023 research review by Dr. Iñigo San-Millán reveals just how central these microscopic powerhouses are to your overall health—and why keeping them healthy should be a top priority for anyone interested in wellness.
Think of mitochondria as the power plants of your body. Every single cell in your body (except red blood cells) contains these tiny organelles that work around the clock to produce energy. But here's what makes them fascinating: mitochondria weren't always part of human cells. About 1.5 billion years ago, our ancient ancestors' cells essentially "adopted" these energy-producing bacteria, and this partnership became one of the most important evolutionary developments in the history of life on Earth.
This ancient relationship is why mitochondria have their own DNA (separate from the DNA in your cell's nucleus), and it's this delicate partnership that keeps you alive and functioning every single day. When mitochondria work well, you feel energized, recover quickly from exercise, and maintain a healthy metabolism. When they don't, the consequences can be severe.
To understand why mitochondrial health matters so much, it helps to know what these organelles actually do. Your mitochondria take the food you eat—whether that's carbohydrates, fats, or proteins—and convert it into a molecule called ATP (adenosine triphosphate), which is essentially the "energy currency" your body uses for everything from thinking to moving to digesting food.
Here's how the process works in simple terms:
Step 1: Breaking Down Food When you eat carbohydrates, your body breaks them down into a molecule called pyruvate. Fats get broken down into fatty acids. These molecules need to be transported into your mitochondria to be used for energy.
Step 2: The TCA Cycle (Also Called the Krebs Cycle) Once inside the mitochondria, these fuel molecules go through a series of chemical reactions in what's called the TCA cycle (tricarboxylic acid cycle—but you don't need to remember that). This process is like a biological assembly line that extracts energy from your food.
Step 3: The Electron Transport Chain The real magic happens in the electron transport chain, which is located on the inner membrane of your mitochondria. This is where the majority of your ATP is actually produced. Think of it like a hydroelectric dam—hydrogen ions build up on one side of the mitochondrial membrane, and when they flow back through, they generate energy, similar to how water flowing through a dam generates electricity.
What's remarkable is that your mitochondria can use different fuels depending on what's available—carbs when you've just eaten, stored fat when you're between meals, and even lactate (which you might know as "lactic acid") during and after exercise. This flexibility is crucial for maintaining steady energy throughout the day.
Here's where things get serious. Dr. San-Millán's review shows that mitochondrial dysfunction—when these cellular power plants can't work at full capacity—is at the root of many of the most common chronic diseases affecting modern society.
One of the most well-established connections is between mitochondrial dysfunction and type 2 diabetes. Research shows that people with type 2 diabetes have fewer mitochondria in their muscle cells, and the ones they do have don't work as efficiently as they should.
This creates a vicious cycle: When your mitochondria can't efficiently burn fat for energy, fat starts accumulating in your muscle cells. This fat buildup (particularly molecules called ceramides) makes your cells resistant to insulin, the hormone that helps your body manage blood sugar. Insulin resistance is the hallmark of type 2 diabetes and affects an astounding 52% of American adults, either as full diabetes or pre-diabetes.
The research is clear: people with type 2 diabetes and metabolic syndrome show what scientists call "metabolic inflexibility." This means their bodies struggle to switch between burning carbs and burning fat depending on what's needed. In a healthy person, your body should smoothly transition from burning mostly carbs right after a meal to burning mostly fat between meals. When mitochondria are dysfunctional, this switching mechanism breaks down.
Your heart is the most energy-demanding organ in your body, beating roughly 100,000 times every single day. It's no surprise, then, that it contains more mitochondria than almost any other tissue. When mitochondrial function declines in heart cells, the consequences can be devastating.
Research reviewed by Dr. San-Millán shows that in cardiovascular disease, the heart undergoes what's called "metabolic reprogramming." Instead of efficiently burning fat (the heart's preferred fuel), damaged hearts shift toward relying more on glucose and produce less ATP overall. This energy deficit contributes to heart failure and other cardiovascular problems.
Even atherosclerosis (the buildup of plaque in arteries) has been linked to mitochondrial dysfunction. Studies have found that the cells in atherosclerotic plaques have reduced copies of mitochondrial DNA, suggesting these cells aren't getting the energy they need to function properly.
Perhaps one of the most striking findings in recent years is the connection between mitochondrial dysfunction and Alzheimer's disease. Some researchers have even started calling Alzheimer's "Type 3 Diabetes" or "brain diabetes" because of the profound metabolic problems in the brains of affected individuals.
Brain cells in people with Alzheimer's show a diminished ability to take up and use glucose for energy. Since your brain cells (neurons) need enormous amounts of energy to function—they're constantly firing electrical signals and maintaining complex chemical balances—this energy deficit leads to progressive cognitive decline.
Research has also revealed that neurons rely heavily on a fuel called lactate (often incorrectly called "lactic acid"). When the brain's ability to use lactate for energy is impaired, it disrupts the brain's entire bioenergetic system. This is particularly important because lactate is produced by support cells in the brain called astrocytes, which essentially "feed" neurons to keep them functioning. When this metabolic cooperation breaks down, neurons begin to fail.
Cancer represents another dramatic example of mitochondrial dysfunction. Nearly 100 years ago, scientist Otto Warburg observed that cancer cells have a peculiar metabolism: even when oxygen is available, they preferentially use a rapid, inefficient form of energy production called glycolysis, producing large amounts of lactate in the process. This is now known as the "Warburg Effect."
Dr. San-Millán's review highlights recent discoveries showing that cancer cells have significantly more mutations in their mitochondrial DNA compared to normal cells. In one major study examining 20 different types of cancer in 859 patients, an incredible 66% of these cancers carried at least one mutation in their mitochondrial DNA.
This mitochondrial damage forces cancer cells to reprogram their metabolism, relying on rapid glucose consumption and lactate production. This isn't just a side effect—it's thought to be a key factor that allows cancer cells to survive and multiply rapidly.
Understanding what causes mitochondrial dysfunction is crucial because some factors are within your control. Dr. San-Millán's review identifies four major causes:
Some people are born with genetic defects in their mitochondrial DNA. These inherited mitochondrial diseases are relatively rare (affecting about 1 in 5,000 people) and usually cause neurological problems, muscle weakness, and other serious issues from an early age.
However, you can also accumulate genetic damage to your mitochondria over your lifetime. Unlike the DNA in your cell's nucleus (which has multiple protective mechanisms), mitochondrial DNA is more vulnerable to damage. It doesn't have protective proteins called histones, and it sits right next to where reactive oxygen species (more on these in a moment) are produced. This makes it particularly susceptible to accumulating mutations as you age.
Speaking of age, getting older is associated with a decline in mitochondrial function. This isn't just about having fewer mitochondria—it's also about changes in how they work.
Your mitochondria have a quality control system. Damaged parts of mitochondria are supposed to be removed through a process called mitophagy (essentially, cellular recycling), and healthy parts are supposed to fuse together to maintain a healthy mitochondrial network. As we age, this quality control system becomes less efficient. Damaged mitochondrial fragments accumulate, and the balance tips toward more fragmentation and less fusion.
The good news? Research shows that much of this age-related decline can be slowed or even reversed with the right interventions—particularly exercise, which we'll discuss in detail shortly.
This might surprise you, but various bacteria and viruses have evolved clever ways to hijack your mitochondria for their own survival. Many pathogens directly attack mitochondria to weaken your immune response and create an environment where they can multiply.
For example:
The SARS-CoV-2 virus (which causes COVID-19) is a particularly relevant example. Research, including Dr. San-Millán's own work, has shown that people suffering from "long COVID" or post-acute sequelae of COVID-19 (PASC) show profound metabolic dysregulation. These patients—even those who were previously healthy and active—show an extremely poor capacity to oxidize fats and clear lactate, suggesting significant mitochondrial dysfunction that persists long after the initial infection.
This finding has important implications: while mitochondrial function normally recovers after an infection clears, some viral infections may cause long-lasting damage that requires targeted rehabilitation (again, primarily through exercise).
Here's perhaps the most important finding from Dr. San-Millán's review: physical inactivity may be the single most significant, modifiable cause of mitochondrial dysfunction in modern society.
The evidence is striking. Studies on bed rest—where healthy people are confined to bed for just a few weeks—show rapid and dramatic declines in mitochondrial function:
Perhaps most telling: the changes caused by bed rest also included modifications to DNA methylation (chemical markers that control gene expression) in the gene that codes for PGC-1α, a master regulator of mitochondrial biogenesis (the creation of new mitochondria). In other words, inactivity doesn't just reduce your current mitochondrial function—it can actually change how your genes are expressed in ways that make it harder to build new, healthy mitochondria.
Dr. San-Millán makes a powerful point: we've normalized physical inactivity in modern society to the point where we think of exercise as an "intervention." But from an evolutionary perspective, it's actually the opposite—regular physical activity is the natural state humans evolved for, and sitting still all day is the real intervention. Our genes still expect us to move, and when we don't, our mitochondria decline.
You've probably heard about "antioxidants" and "free radicals" before, usually in the context of antioxidant supplements being marketed as anti-aging miracles. The reality is more nuanced and more interesting.
Reactive oxygen species (ROS)—which include free radicals—are constantly produced by your mitochondria as a natural byproduct of energy production. About 0.4% of the oxygen you breathe gets converted into these reactive molecules, primarily at a part of the mitochondrial electron transport chain called Complex I.
For decades, ROS were thought to be purely harmful, causing aging and disease through oxidative damage. But more recent research has revealed that at normal physiological levels, ROS are actually essential signaling molecules. They're involved in:
This beneficial effect of low levels of cellular stress is called "mitohormesis" or "oxidative eustress." It's similar to how the stress of exercise makes you stronger—a little bit of ROS production actually signals your body to build more robust cellular defenses.
The problem comes when ROS production exceeds your body's ability to neutralize them using antioxidant systems like superoxide dismutase (SOD), catalase, and glutathione. When this balance tips toward too much ROS, oxidative stress occurs, leading to damage of proteins, lipids, and DNA.
Here's where things get complicated: Does mitochondrial dysfunction cause excessive ROS production, or does excessive ROS production cause mitochondrial dysfunction? The answer appears to be: both. This creates a vicious cycle. Damaged mitochondria produce more ROS, which causes more mitochondrial damage, which produces even more ROS, and so on.
This is one reason why simply taking antioxidant supplements hasn't proven to be the magic bullet many hoped. If you suppress ROS production too much, you interfere with the beneficial signaling functions and potentially with the mitohormetic responses to exercise. The goal isn't to eliminate ROS entirely but to maintain them at healthy levels—and the best way to do that appears to be through improving overall mitochondrial health rather than just trying to mop up free radicals after they're produced.
If there's one overwhelming message from Dr. San-Millán's review, it's this: exercise is the most powerful intervention we have for improving mitochondrial function. Not supplements. Not drugs. Exercise.
The evidence is comprehensive and convincing:
When you exercise regularly, especially at moderate intensities, your body responds by creating more mitochondria (a process called mitochondrial biogenesis). This isn't just about quantity—the quality of these mitochondria improves too.
Studies show that:
Even more encouraging: the mitochondrial damage caused by inactivity or aging can be substantially reversed with exercise. In the bed rest study mentioned earlier, when participants returned to normal activity and training for four weeks, an incredible 82% of the genetic changes caused by bed rest were reversed.
This means that even if you've been inactive for years (or decades), your mitochondria retain the capacity to improve when you start moving again. It's never too late to start building better health habits, even with short mini-workouts.
Dr. San-Millán emphasizes the concept of "metabolic flexibility"—your body's ability to efficiently switch between burning carbohydrates and fats depending on what's available and what's needed. This flexibility is tightly linked to mitochondrial health.
When your mitochondria are functioning well, your body can:
People with metabolic diseases like type 2 diabetes lose this flexibility. Their bodies struggle to burn fat efficiently and rely too heavily on glucose. This is both a cause and a consequence of mitochondrial dysfunction.
Exercise—particularly a mix of moderate-intensity steady-state exercise and some higher-intensity work—is the most effective way to restore metabolic flexibility. In fact, Dr. San-Millán and his colleagues have shown that individualized exercise programs can reverse pre-diabetes by improving lactate clearance and fat oxidation capacity.
Dr. San-Millán makes a fascinating point: elite endurance athletes have the highest-functioning mitochondria of any human population. They can produce enormous amounts of energy aerobically, clear lactate incredibly efficiently, and maintain metabolic flexibility across a wide range of intensities.
While most of us aren't trying to become Olympic athletes, we can learn important lessons from how these "perfect human machines" train:
These principles can be adapted for anyone looking to improve their metabolic health, regardless of current fitness level. The key is starting where you are and progressively building your mitochondrial capacity over time.
One of the practical innovations Dr. San-Millán discusses is a methodology for indirectly measuring mitochondrial function through exercise testing. This involves two key measurements:
1. Fat Oxidation (FATox or FATmax) This test measures how efficiently your body can burn fat at different exercise intensities. People with healthy mitochondria can burn fat very efficiently, even at moderate exercise intensities. People with mitochondrial dysfunction show reduced fat-burning capacity.
2. Lactate Clearance By measuring blood lactate levels during incremental exercise, clinicians can assess how well your mitochondria are oxidizing lactate. Healthy mitochondria clear lactate efficiently; dysfunctional mitochondria allow it to accumulate.
Together, these measurements provide a window into your metabolic health and can help guide individualized exercise prescriptions. If your testing shows poor fat oxidation and lactate clearance, it suggests mitochondrial dysfunction, and training can be specifically targeted to improve these capacities.
This is the concept of "exercise as medicine"—using exercise as a precise, personalized intervention rather than just generic advice to "move more."
Dr. San-Millán's review makes clear that we're still in the early stages of understanding mitochondrial dysfunction and its role in disease. While the connections are becoming clearer, many questions remain:
What's already clear is that mitochondrial health deserves a central place in how we think about preventing and treating chronic disease. The old model of waiting until someone develops diabetes or heart disease and then treating symptoms isn't working—these conditions have reached epidemic proportions despite our best medical treatments.
A new model focused on maintaining and improving mitochondrial function throughout life—primarily through regular physical activity, but potentially supplemented by other interventions—offers a path forward. As Dr. San-Millán writes, physical activity should be considered the natural human state, and sedentary living the aberration that needs correcting.
Based on the research findings in Dr. San-Millán's review, here are specific, actionable steps you can take to support your mitochondrial health:
Make regular exercise non-negotiable. Aim for at least 150 minutes per week of moderate-intensity activity—think of a pace where you're working but could still hold a conversation. This is the sweet spot for building mitochondrial capacity. Consistency is more important than intensity, especially when you're starting out. Even if you're completely new to exercise, beginning with simple walking and gradually building up can lead to significant mitochondrial improvements.
Include both steady-state and higher-intensity work. While most of your exercise should be at moderate intensities that directly target mitochondrial development, including some higher-intensity sessions (about 1-2 times per week) can complement this by improving your mitochondrial efficiency and metabolic flexibility. Just don't make the mistake of thinking every workout needs to be an intense, 1000-calorie-burning session—that approach can actually be counterproductive.
Prioritize protein and don't fear healthy fats. Your mitochondria need the right building blocks to function properly. Adequate protein supports mitochondrial biogenesis, while healthy fats provide an important fuel source that well-functioning mitochondria should be able to oxidize efficiently. Don't fall for extreme dietary approaches; your body needs a variety of nutrients. Eating healthy doesn't have to be complicated or expensive.
Avoid prolonged inactivity. Remember that just 9-14 days of bed rest can cause significant mitochondrial decline. Even if you can't do formal exercise every day, break up long periods of sitting. Set a timer to stand and move for a few minutes every hour. Take the stairs instead of the elevator. Park farther away. These small movements throughout the day help maintain mitochondrial function.
Consider metabolic testing if you have risk factors. If you have pre-diabetes, metabolic syndrome, persistent fatigue, or a family history of metabolic diseases, consider getting metabolic testing done (FATmax and lactate testing) to assess your mitochondrial function. This can provide a baseline and help guide your exercise programming. Many sports performance labs and some progressive medical clinics now offer these services.
Be patient and consistent. Mitochondrial biogenesis doesn't happen overnight. The studies showing significant improvements typically involved 8-12 weeks of consistent training. Give your body time to adapt. The genetic changes that improve mitochondrial function take weeks to fully manifest, but remember: 82% of the genetic expression altered by inactivity can be restored with just four weeks of training.
Focus on recovery and sleep. While the review focuses primarily on exercise, it's worth noting that mitochondria also need recovery time to adapt and repair. Getting adequate sleep, managing stress, and allowing recovery days in your training schedule all support the mitochondrial adaptations you're working to build.
Dr. San-Millán's comprehensive review reveals that mitochondrial dysfunction sits at the intersection of many of our most pressing health challenges—type 2 diabetes, cardiovascular disease, Alzheimer's, cancer, and accelerated aging. While some factors affecting mitochondrial health (like genetic mutations or aging) are largely beyond our control, physical activity represents a powerful, proven intervention that's accessible to virtually everyone.
The research is unequivocal: regular exercise is the most effective way to build, maintain, and restore mitochondrial function. This isn't about becoming an elite athlete or spending hours in the gym every day. It's about consistent, moderate-intensity physical activity that gives your mitochondria the stimulus they need to thrive.
In many ways, taking care of your mitochondria is taking care of your health at the most fundamental cellular level. When your mitochondria work well, everything else—your energy, your metabolism, your cognitive function, your resilience to disease—tends to follow.
The ancient partnership between our cells and these bacterial-origin powerhouses has served us well for 1.5 billion years. Honoring that relationship by moving our bodies regularly might be one of the simplest and most profound things we can do for our health.
Understanding how your mitochondria work is just the beginning. If you're looking for a structured, science-based approach to building lasting health habits—including exercise, nutrition, and lifestyle practices that support your cellular health—consider exploring our comprehensive health and wellness course.
We've designed the program to take complex exercise science and nutrition research (like the mitochondrial function studies we've discussed here) and translate it into practical, actionable strategies you can implement immediately. Whether you're just starting your wellness journey or looking to optimize your current routine, our course provides the knowledge and tools to make sustainable changes that support your health at every level—from your mitochondria to your daily energy and long-term disease prevention.
Learn more about building your personalized wellness plan →
San-Millán, I. (2023). The key role of mitochondrial function in health and disease. Antioxidants, 12(4), 782. https://doi.org/10.3390/antiox12040782
Acetyl-CoA — A molecule that enters the Krebs cycle (TCA cycle) and serves as the common starting point for the oxidation of carbohydrates, fats, and some amino acids. It's like the universal fuel ticket that lets different nutrients enter the mitochondrial energy production system.
Angiogenesis — The process by which new blood vessels form from existing ones. This is important for delivering oxygen and nutrients to tissues, and it's one of the processes that's regulated by the signaling functions of reactive oxygen species (ROS).
Antioxidants — Molecules that neutralize reactive oxygen species (ROS) and protect cells from oxidative damage. Your body produces its own antioxidants (like superoxide dismutase and glutathione), and you can also get them from foods.
ATP (Adenosine Triphosphate) — The main energy currency in your body. When your cells need energy to do anything—contract a muscle, fire a nerve signal, transport molecules—they "spend" ATP by breaking one of its chemical bonds, which releases energy.
Atherosclerosis — The buildup of fatty plaques in the walls of arteries, which can lead to heart attacks and strokes. Research shows that cells in these plaques have damaged mitochondria.
Bed Rest Studies — Research studies where healthy volunteers are confined to bed for days or weeks to study the effects of inactivity on metabolism, muscle, bone, and other body systems.
Biogenesis (Mitochondrial) — The creation of new mitochondria inside cells. This process is stimulated by exercise and controlled by genes like PGC-1α.
Cardiolipin (CL) — A specialized fat molecule (phospholipid) found only in the inner membrane of mitochondria. It's essential for proper mitochondrial function, and damage to cardiolipin is associated with various diseases.
Ceramides — A type of fat molecule that accumulates in muscle and other tissues when mitochondria can't burn fat efficiently. Ceramide accumulation is strongly linked to insulin resistance.
Citrate Synthase (CS) — An enzyme involved in the first step of the Krebs cycle (TCA cycle). Scientists often measure citrate synthase activity as an indirect indicator of how many functional mitochondria are present in a tissue.
Complex I, II, III, IV — Four large protein structures embedded in the inner mitochondrial membrane that make up the electron transport chain. They work together like a series of generators to create the energy gradient that drives ATP production. Complex I is also the main site where reactive oxygen species are produced.
CPT1/CPT2 (Carnitine Palmitoyltransferase 1 and 2) — Proteins located on the outer and inner mitochondrial membranes that transport long-chain fatty acids into mitochondria so they can be burned for energy. When these transporters don't work properly, fat oxidation is impaired.
Electron Transport Chain (ETC) — The series of protein complexes (Complex I through IV) in the inner mitochondrial membrane that transfer electrons and pump hydrogen ions to create the energy gradient used to produce ATP. This is where most of your cellular energy is actually generated.
Eukaryotic Cells — Cells that have a nucleus and other membrane-bound organelles (like mitochondria). All animals, plants, fungi, and many single-celled organisms are made of eukaryotic cells.
Fat Oxidation (FATox) — The process of breaking down fatty acids in mitochondria to produce energy. The rate at which you can oxidize fat (often measured as FATmax) is an important indicator of metabolic health and mitochondrial function.
Fission (Mitochondrial) — The process by which mitochondria split into smaller fragments. This is part of the quality control system that isolates damaged portions of mitochondria for removal.
Fusion (Mitochondrial) — The process by which separate mitochondria join together into larger, interconnected networks. Fusion helps distribute healthy mitochondrial components and maintain the mitochondrial network.
Glycolysis — The breakdown of glucose into pyruvate, which occurs in the main body of the cell (not in the mitochondria). This process produces a small amount of ATP and is the first step in using carbohydrates for energy.
Hydrogen Ions (H+) — Positively charged hydrogen atoms that are pumped across the mitochondrial membrane during the electron transport chain. When these ions flow back across the membrane, they drive the production of ATP—similar to how water flowing through a dam generates electricity.
Insulin Resistance — A condition where cells don't respond properly to insulin, the hormone that helps move glucose from the blood into cells. This forces the body to produce more and more insulin, eventually leading to type 2 diabetes. Mitochondrial dysfunction and fat accumulation in muscle are major causes of insulin resistance.
Krebs Cycle — See TCA Cycle.
Lactate (Often Incorrectly Called "Lactic Acid") — A molecule produced when pyruvate is converted in the cytoplasm, often during high-intensity exercise or when glycolysis is running faster than mitochondria can keep up. Contrary to popular belief, lactate is actually an important fuel for mitochondria, not just a waste product. Healthy mitochondria can efficiently oxidize lactate for energy.
Lactate Clearance — The ability to remove lactate from the blood and tissues by oxidizing it in mitochondria. Poor lactate clearance is a sign of mitochondrial dysfunction.
LDH (Lactate Dehydrogenase) — The enzyme that converts pyruvate into lactate (and vice versa). There are different forms of this enzyme in different tissues, with some favoring lactate production and others favoring lactate oxidation.
Metabolic Flexibility — The ability of your body to efficiently switch between burning different fuels (particularly carbohydrates and fats) depending on what's available and what's needed. Loss of metabolic flexibility is characteristic of metabolic diseases like type 2 diabetes.
Metabolic Reprogramming — A shift in how cells produce energy, often seen in disease states. For example, cancer cells often reprogram their metabolism to rely heavily on glycolysis instead of mitochondrial oxidation (the Warburg Effect).
Metabolic Syndrome — A cluster of conditions—including high blood pressure, high blood sugar, excess abdominal fat, and abnormal cholesterol levels—that together increase the risk of heart disease, stroke, and type 2 diabetes. Mitochondrial dysfunction is thought to play a central role.
Mitochondrial DNA (mtDNA) — The small, circular piece of DNA that mitochondria inherited from their bacterial ancestors. It contains only 37 genes (compared to the roughly 20,000 in your nuclear DNA), all of which code for proteins involved in energy production.
Mitochondrial Pyruvate Carrier (MPC) — A protein that transports pyruvate (the end product of glucose breakdown) across the mitochondrial membrane so it can be oxidized for energy.
Mitohormesis — The beneficial adaptive response triggered by mild mitochondrial stress (such as the reactive oxygen species produced during exercise). Like other forms of hormesis, a small amount of stress makes you stronger and more resilient.
Mitophagy — The selective removal and recycling of damaged mitochondria by the cell's autophagy (self-eating) system. This quality control process is essential for maintaining a healthy population of mitochondria.
NADH and FADH2 — Molecules that carry high-energy electrons from the Krebs cycle to the electron transport chain. They're like rechargeable batteries that get "charged" during the Krebs cycle and then "discharge" their energy in the electron transport chain to make ATP.
Nuclear DNA (nuDNA) — The DNA contained in the cell's nucleus (as opposed to mitochondrial DNA). While mitochondria have their own DNA, most of the genes that control mitochondrial function are actually in the nuclear DNA.
Oxidative Phosphorylation (OXPHOS) — The process by which ATP is produced in mitochondria using oxygen. This is the main energy-producing system in healthy cells and is much more efficient than glycolysis.
Oxidative Stress — The condition that occurs when the production of reactive oxygen species (ROS) exceeds the body's ability to neutralize them with antioxidants. This leads to damage to proteins, lipids, and DNA.
PDH (Pyruvate Dehydrogenase) — The enzyme complex that converts pyruvate into Acetyl-CoA inside the mitochondria, allowing the energy from glucose to enter the Krebs cycle.
PGC-1α (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha) — Often called the "master regulator" of mitochondrial biogenesis. When this protein is activated (particularly by exercise), it triggers a cascade of events that leads to the creation of new mitochondria.
Post-Acute Sequelae of COVID-19 (PASC) — The medical term for "long COVID"—the persistent symptoms some people experience long after recovering from a SARS-CoV-2 infection. Research shows many PASC patients have significant mitochondrial dysfunction.
Prokaryotic Cells — Simple cells without a nucleus or other membrane-bound organelles, like bacteria. Mitochondria are thought to have evolved from ancient prokaryotic cells that were engulfed by eukaryotic cells.
Pyruvate — A three-carbon molecule that's the end product of glycolysis. It can either be transported into mitochondria and converted to Acetyl-CoA for oxidation, or it can be converted to lactate in the cytoplasm.
Reactive Oxygen Species (ROS) — Highly reactive molecules containing oxygen, including free radicals like superoxide and others like hydrogen peroxide. Produced primarily by mitochondria, ROS at low levels are important signaling molecules, but at high levels cause oxidative stress and cellular damage.
Sepsis — A life-threatening condition where the body's response to infection causes widespread inflammation and organ damage. Research shows that mitochondrial dysfunction plays a key role in the organ failure characteristic of sepsis.
Skeletal Muscle — The type of muscle that moves your skeleton and is under voluntary control (as opposed to cardiac muscle in your heart or smooth muscle in your digestive tract). Skeletal muscle contains vast numbers of mitochondria and is central to metabolic health since it's responsible for about 85% of glucose uptake in response to insulin.
Succinate Dehydrogenase (SDH) — An enzyme that's part of both the Krebs cycle and the electron transport chain (Complex II). Like citrate synthase, SDH activity is often measured as an indicator of mitochondrial content and function.
Superoxide Dismutase (SOD) — An antioxidant enzyme that converts superoxide radicals into hydrogen peroxide, which can then be further broken down by other antioxidants. SOD is one of the body's primary defenses against oxidative stress.
TCA Cycle (Tricarboxylic Acid Cycle) — Also called the Krebs cycle, this is the series of chemical reactions in the mitochondrial matrix that extracts energy from Acetyl-CoA derived from carbohydrates, fats, and proteins. The TCA cycle produces the NADH and FADH2 that carry energy to the electron transport chain.
Type 2 Diabetes (T2D) — A metabolic disease characterized by high blood sugar levels due to insulin resistance (cells don't respond properly to insulin) and eventually insufficient insulin production. About 52% of American adults have either pre-diabetes or type 2 diabetes, and mitochondrial dysfunction is central to its development.
Warburg Effect — The observation that cancer cells often rely heavily on glycolysis for energy production even when oxygen is available, producing large amounts of lactate. Named after Otto Warburg, who discovered this phenomenon nearly 100 years ago. This metabolic reprogramming is now understood to be related to mitochondrial dysfunction in cancer cells.
