Mitochondria

What they actually do, which is not just energy

Energy is the headline. Food and oxygen go in, and a chain of protein complexes in the inner membrane strips electrons off and uses them to drive the manufacture of ATP, the molecule every cell spends to do anything at all. Coenzyme Q10 is one of the carriers in that chain, which is why it appears in the statin passage in the Muscle section.

Three other jobs explain why mitochondria keep turning up in sections that look unrelated to each other.

They start every steroid hormone you make. The first step, the one that converts cholesterol into the molecule everything else is built from, happens inside a mitochondrion. Not near one. Inside. Testosterone, oestradiol, cortisol, aldosterone and DHEA all begin in there. Which means the cells doing the most hormone production, in your adrenal glands and your testes or ovaries, are packed with mitochondria for that reason as much as for energy.

They build haem. The ring that holds the iron at the centre of haemoglobin is assembled in a sequence that starts inside the mitochondrion, leaves, and comes back in for the final step where the iron is inserted. Mitochondria also assemble the iron-sulphur clusters that other enzymes need, including some in the chain that makes ATP. So iron and mitochondria are not two separate topics. The Iron section says iron deficiency makes you tired long before it makes you anaemic, and this is where that happens.

They decide when a cell dies. When a cell is damaged beyond repair, mitochondria release a protein into the rest of the cell that triggers a controlled shutdown. The same structure that powers the cell holds the switch that ends it.

Why they turn up everywhere on this page, and everywhere else

Go back through what you have read and the thread runs through most of it.

Thyroid. Thyroid hormone works partly by instructing cells to build more mitochondria and to run the ones they have less efficiently, deliberately wasting some energy as heat. That is a large part of why an underactive thyroid slows everything down and an overactive one burns through fuel and leaves you hot.

Blood sugar. Muscle disposes of most of the glucose from a meal, mostly by storing it as glycogen rather than burning it, and what does get burned is burned in mitochondria. Reduced mitochondrial capacity often travels with insulin resistance, and people with the same insulin sensitivity can have very different mitochondrial capacity.

Liver. Fat accumulating in a liver is partly a question of whether its mitochondria can process what is arriving. When they cannot keep up, fat is stored instead.

Fat loss. Fat is not burned in some general sense. It is broken down inside mitochondria, and long-chain fats cannot get in on their own. They need a shuttle, and the molecule that carries them is carnitine. That is the actual mechanism behind every "fat burner" containing L-carnitine, and it is also why those products disappoint. Getting more carnitine into muscle from a capsule is genuinely difficult, and in people who are not deficient it does not reliably do anything to body fat.

Brain. Your brain is about 2% of your body weight and takes around 20% of your energy. Neurons cannot store fuel and cannot pause. Concentration, memory formation and clear thinking are all energetically expensive, which is why brain fog is a real complaint even when it is a vague one, and why it appears in almost every condition on this page.

Gut. The cells lining your colon run largely on butyrate, a short-chain fatty acid your gut bacteria produce from fibre, and they burn it in mitochondria. It is one of the few places in the body fed directly by something living inside you. The same bacteria are the reason one of the supplements described further down this page exists at all.

Fertility. An egg contains more mitochondria than any other cell in the body, by a wide margin, and the quality of those mitochondria is one of the things that changes as a woman ages. At the other end, the midpiece of a sperm is essentially a sleeve of mitochondria wrapped around the tail, because swimming is expensive. Both halves of fertility are mitochondrial problems in part.

Nutrients. The B vitamins are cofactors in the reactions feeding the chain. The selenium in the thyroid section sits at the active site of enzymes cleaning up what the chain leaks. Magnesium, from the minerals section, is required for ATP to function at all.

The claim that mitochondria are involved in everything

You will see this said, usually by somebody selling something. It is closer to true than most marketing claims and it still needs handling carefully.

Mitochondrial dysfunction has been described in neurodegenerative disease, heart failure, type 2 diabetes, fatty liver, kidney disease, several cancers, chronic fatigue states, and in ageing itself, where it is one of the recognised hallmarks. That is a real and repeated observation across a very large literature.

What is much harder is knowing what it means. A cell in trouble has mitochondria in trouble, and separating the cause from the consequence has been done properly in very few of those conditions. Finding damaged mitochondria in a diseased tissue does not tell you which came first.

So the defensible version is this. Mitochondria are downstream of almost everything and upstream of a great deal, they are involved in most chronic disease, and "involved" is carrying a lot of weight in that sentence. It is a reason to take them seriously. It is not a reason to believe anybody who says they can fix yours.

What you can measure, and it is very little

Nothing on any blood panel sold anywhere measures how well your mitochondria are working. Not ours, not anybody's.

The closest routine number is lactate. When the chain cannot keep up with demand, pyruvate is converted to lactate instead, so lactate rises. It is crude, it goes up for plenty of reasons including simply having exercised, and it says nothing about somebody sitting still and feeling fine.

Real assessment means a muscle biopsy with the respiratory chain enzymes measured directly, or genetic testing of mitochondrial and nuclear DNA. Both are hospital investigations for people with a specific clinical picture, not something to buy.

So if you are offered a panel described as measuring mitochondrial function, ask what it actually measures and what it was validated against. The reference methods are a biopsy and a genome. Very little sold on the internet has been compared with either.

The one thing that reliably works

Exercise builds mitochondria. Not metaphorically, and not by a small amount.

The mechanism is reasonably well mapped. When muscle is repeatedly asked to produce energy faster than it comfortably can, the cell notices, through sensors that read falling energy charge and rising calcium. That switches on a protein called PGC-1alpha, which moves into the nucleus and turns on the genes for building new mitochondria. It is generally described as the master regulator of the process, although animals engineered to lack it in muscle still build mitochondria in response to exercise, so it is not the only route in.

Intensity and volume are not doing the same job, which is why the argument about which is better is the wrong argument.

High-intensity intervals are among the strongest single stimuli anybody has measured. In a 12-week trial in previously sedentary adults, intervals produced the largest gain in the respiratory capacity of muscle mitochondria of the training types compared, in younger and older people alike. Insulin sensitivity improved too, but it also improved with training that did not change mitochondrial capacity at all. It is also time-efficient, which is the practical argument for it.

Lower-intensity endurance work, the sort people now call zone 2, is the volume driver. It is the intensity you can sustain long enough to accumulate real time, it is close to where the rate of fat oxidation peaks, and it carries far less recovery cost, which is what lets you do enough of it. Nobody has shown intervals make it redundant.

Strength training does something different and it should not be undersold for the wrong reason. In that same trial, resistance training alone did not increase the respiratory capacity of muscle mitochondria, although it did raise the amount of mitochondrial protein. What it does is increase the amount of muscle, and muscle is where most of the glucose from your meals is disposed of and where most of your mitochondria live. More muscle means a larger total pool and better glucose handling, even at unchanged mitochondrial density. The honest summary is that strength work is not the most direct mitochondrial stimulus, but leaving it out is a mistake due to its numerous other benefits.

And there is a ceiling, which almost nobody mentions. A 2021 study progressively increased interval training volume in healthy, already active people. Mitochondrial respiration improved, then plateaued, then went backwards, and glucose tolerance fell with it. Content had not dropped. The mitochondria they had were working worse. Reducing the training load reversed it.

That is a bell-shaped curve rather than a straight line. More is better until it is not, and the point where it turns is not signalled by anything you can measure in blood.

The rest of it, briefly

Sleep is when a large share of cellular repair happens, including the clearing of damaged mitochondria and their replacement. The evidence in humans is less mapped than the exercise evidence, but nothing about chronic short sleep looks good for this system.

Walking is not the same stimulus as training and it is not nothing either. The difference between sedentary and lightly active is, in population terms, larger than most of the differences people spend money chasing.

Not living in permanent energy surplus. Continuously oversupplying a cell with fuel it does not need appears to be part of how this system degrades. That is the least satisfying item on the list and probably one of the more important.

The supplements, and what the trials found

Mitochondrial health is one of the most heavily marketed ideas in the supplement industry, so this needs saying carefully.

The NAD precursors, nicotinamide riboside and nicotinamide mononucleotide, are the biggest sellers. The mechanism is real. NAD carries electrons into the chain, levels appear to fall with age, and taking either compound reliably raises the NAD in your blood, with the higher doses of nicotinamide riboside roughly doubling it. That part is properly demonstrated. However, what we often see is that these supplements may not contain the active ingredients as they can break down during storage and transit.

Then the trials measured whether anything happened. A systematic review published in 2026 gathered 113 studies including 28 randomised trials in humans, and found the biomarker moves reliably while metabolic, vascular and performance outcomes are mixed. A separate 2025 meta-analysis looking specifically at muscle in older adults concluded the evidence does not support these compounds for preserving muscle mass or function at all. The 2026 review also found no outcome trials at all behind intravenous NAD, which is sold in clinics across this country at considerable expense.

Which makes this the clearest example on the whole page of the thing this guide keeps returning to. A number moved. That is not the same as something happening.

Urolithin A is the most interesting of the group. It is not in food. Your gut bacteria make it from compounds in pomegranates, walnuts and some berries. Around 1 in 10 people carry no bacteria that can, and how much the rest produce varies enormously, which is the argument for selling it as a supplement. It works on the process cells use to clear out damaged mitochondria and replace them. Roughly 10 randomised human studies exist, totalling about 400 people, which is a small pile and a smaller one than sits behind the NAD precursors.

Coenzyme Q10 is covered in the Muscle section, where a trial gave 400 mg a day for 8 weeks and then took muscle biopsies. Muscle levels did not rise, mitochondrial function did not change, symptoms did not improve.

L-carnitine is described above. Real mechanism, poor delivery, unconvincing results in people who are not deficient.

The shape is consistent. The mechanisms are genuine, the biomarkers respond, and the outcomes people are buying these for have mostly not been demonstrated. That is not the same as saying none of it works. It is saying that being sold something is not evidence, and that the intervention with the best data behind it by a wide margin is a pair of trainers.

One thing this guide is not going to cover

There is a category of compounds aimed directly at mitochondria that circulates in performance and longevity circles, mostly peptides, some of them genuinely interesting and a few of them in real clinical trials for inherited mitochondrial disease.

They are not licensed medicines in the UK. Which means nobody can tell you what is in the vial you were sold, what dose you took, or what it does over years, because the studies that would answer that have not been done in people like you.

We are not going to write about them, and the reason is the same one that runs through this whole site. Everything else here is either established physiology or a named source you can go and check. That category has neither, and pretending otherwise to seem current would undo the point of the page.

What changes when they are struggling

Inherited mitochondrial disease is a real and serious group of conditions, and it presents in the tissues with the highest energy demand. Muscle weakness and exercise intolerance out of proportion to effort, hearing and vision problems, seizures, heart muscle disease, diabetes combined with deafness. It is uncommon, usually diagnosed in childhood or early adult life, and it is not what tiredness is.

The far more common situation is mitochondrial capacity declining gradually with age and with inactivity. It produces no diagnosis and shows on no test. It shows as less of everything. Less endurance, slower recovery, less tolerance for training that used to be easy, and a body that handles a large meal worse than it did 10 years ago.

There is no marker for that on your report. What there is, is the fact that it responds to being used.