Every day, a healthy adult makes around 50 kg of ATP, the molecule that supplies cells with energy, according to a 2015 review. Most comes from mitochondria. Here is how a mitochondrion works, what changes with age and what studies suggest helps maintain it.
Key takeaways
- A glucose molecule fully oxidised through mitochondria yields up to 33 ATP, compared with 2 from glycolysis alone (a 2017 theoretical calculation).
- Mitochondrial DNA, around 16,600 base pairs long, carries 37 genes and is almost always inherited from the mother.
- According to a 2008 study, ATP production by muscle mitochondria falls with age in sedentary people, but not in endurance athletes.
- In a 2017 trial, 12 weeks of interval training increased muscle mitochondrial respiration by 69% in 9 adults aged 65 to 80.
What is a mitochondrion?
A mitochondrion is an organelle: a specialised cellular compartment bounded by two membranes, which uses oxygen to convert energy from food into ATP. Visible under a light microscope, it often forms a network of tubes with its neighbours, constantly dividing and fusing.
The image of the “powerhouse of the cell” dates to 1957. A 2023 review considers it too simple and lists dozens of functions.
Two membranes, cristae and a matrix
The outer membrane is porous: channels allow ions and small molecules through. The tightly sealed inner membrane allows through only what its transporters select; an electrical difference of around 180 millivolts is maintained across it. It folds into cristae, where the respiratory chain and ATP synthase are concentrated. At the centre, the protein-rich matrix houses mitochondrial DNA and the Krebs cycle.
Separate DNA, inherited from the mother
A mitochondrion has its own DNA: a circular molecule around 16,600 base pairs long, present in several copies. Its 37 genes encode 13 proteins of the respiratory chain and ATP synthase, and 24 RNAs used to make them. This DNA is inherited from the mother.
Mutations in this DNA, or in nuclear genes, cause mitochondrial diseases: rare genetic disorders with varied symptoms that require specialised medical follow-up.
An ancient bacterium that became an organelle
The mitochondrion descends from a bacterium related to alphaproteobacteria, engulfed by another cell around 1.6 billion years ago: this is the endosymbiotic theory. It retains traces of this origin, such as its own ribosomes and respiratory complexes very similar to those of bacteria.
How many mitochondria are there in a cell?
This depends on the tissue. Since mitochondria often form a network, researchers usually measure mitochondrial DNA copy number, with several copies per mitochondrion: generally 100 to 5,000 per cell, according to a 2023 review. A heart muscle cell contains more than 6,000 on average, and a white blood cell around 350.
How does a mitochondrion produce ATP?
It transfers electrons removed from nutrients such as glucose, fatty acids and some amino acids to oxygen, using the released energy to make ATP. Here are the steps for glucose.
| Stage | Where | What happens | Key molecules |
|---|---|---|---|
| Glycolysis | Cytoplasm | Glucose is split into two pyruvates; gain of 2 ATP | Glucose, pyruvate, NADH |
| Krebs cycle | Matrix | Pyruvate, converted to acetyl-CoA, is oxidised to CO2 | Acetyl-CoA, NADH, FADH2 |
| Respiratory chain | Inner-membrane cristae | Electrons travel to oxygen; protons are pumped | Complexes I to IV, coenzyme Q10, cytochrome c |
| ATP synthase | Inner-membrane cristae | The return flow of protons turns the motor that makes ATP | ADP, phosphate, ATP |
Complex I receives electrons from NADH, and complex II from succinate, an intermediate of the Krebs cycle. Coenzyme Q10 carries them to complex III, then cytochrome c to complex IV, which transfers them to oxygen to form water. See also the difference between NAD+ and NADH.
Complexes I, III and IV pump protons out of the matrix. Flowing back through ATP synthase, they turn a ring of 8 subunits, the rotor of a motor that assembles ATP. In total, complete oxidation of one glucose yields a maximum of 33.45 ATP, according to a 2017 calculation.
Free radicals, calcium and heat: mitochondria's other roles
As electrons travel, a few escape and react with oxygen, forming reactive oxygen species, mainly at complexes I and III. Long regarded as mere waste products, they also act as signals. In a human trial, high-dose antioxidants even erased some training benefits (see oxidative stress and antioxidants).
Mitochondria also take up and release calcium, trigger programmed cell death by releasing cytochrome c, and produce heat when a protein such as UCP1 uncouples respiration from ATP production. In the adrenal glands and gonads, they carry out the first step of steroid hormone synthesis from cholesterol.
How does a cell maintain its mitochondria?
Through constant quality control. Mitochondria continuously fuse and divide, which may allow a damaged section to be isolated. When one loses its electrical potential, the PINK1 protein accumulates on its surface and recruits Parkin, which marks it for destruction: this is mitophagy. Conversely, biogenesis, coordinated by the PGC-1α protein, multiplies existing mitochondria.
What does age change in mitochondria?
Their capacity to produce ATP declines, but inactivity contributes substantially. A 2008 study compared 42 young adults aged 18 to 30 and older adults aged 59 to 76, either sedentary or endurance-trained. Among sedentary participants, the older adults' muscle mitochondria produced less ATP. Among athletes, the age-related difference was not significant, although older participants still had less mitochondrial DNA.
Not all tissues age in the same way. In a 2016 study of 152 autopsied people aged from 3 days to 96 years, mitochondrial DNA copies decreased with age in muscle, particularly in men, but increased in the liver.
Mitochondrial DNA mutations also accumulate with age. In animals, mitophagy slows in one area of the brain and NAD+, which carries electrons towards the respiratory chain, decreases in several tissues. In humans, this decline depends on the tissue (see NAD+ and its changes with age).
The mitochondrial theory of ageing needs qualification
According to the free radical theory proposed in 1956, damage caused by oxidants would age the body. Mitochondria, which produce oxidants, became central to this idea. In animals, neutralising these oxidants extended life in some models but not others, and more oxidants sometimes extended it.
“Mutator” mice, whose mitochondrial DNA accumulates errors, age prematurely. But their mutations differ in type and number from those of normal ageing: the role of mutations in ageing remains debated.
Maintaining mitochondria: what do studies show?
Physical activity is the best-demonstrated approach in humans at any age: it stimulates mitochondrial biogenesis.
Endurance and interval training
In a 2003 trial, 65 adults aged 21 to 87 completed 16 weeks of endurance training, compared with 37 controls. The activity of two muscle mitochondrial enzymes increased by 45 to 76%, regardless of age.
In 2017, a trial randomly assigned adults aged 18 to 30 and 65 to 80 to three 12-week programmes. Interval training combined three cycling sessions per week, with 4 intervals of 4 minutes above 90% of maximal oxygen consumption, and two walking sessions. It increased maximal muscle mitochondrial respiration by 69% in the 9 older participants and 49% in the 14 younger participants. The moderate cycling and strength-training programme had a significant effect only in the younger group (+38%), and strength training alone in neither group.
Training also increases muscle NAMPT, the key enzyme in NAD+ recycling: see the approaches studied for increasing NAD+.
Sleep and diet
Insufficient sleep may affect mitochondria. In a small 2021 trial with 24 young men in three groups of 8, five nights with 4 hours in bed reduced glucose tolerance compared with the group sleeping 8 hours. Muscle mitochondrial respiration also fell by around 18%, but without a significant difference from that group. These reductions were not observed in the group that added three interval-training sessions.
For diet, a 2007 trial tested 6 months of calorie restriction in 36 adults with overweight. Eating 25% fewer calories increased muscle mitochondrial DNA by 35%, compared with +21% with restriction plus exercise and +2% in controls, without changing mitochondrial enzyme activity. Such restriction should not be improvised: seek advice from a health professional.
Vitamins, minerals and supplements: what can be claimed?
Fifteen vitamins and minerals have an authorised claim for energy-yielding metabolism: pantothenic acid, biotin, calcium, copper, iron, iodine, magnesium, manganese, niacin, phosphorus, riboflavin, thiamine and vitamins B6, B12 and C. The product must provide at least a “source” of the nutrient as defined by regulations.
Several work inside mitochondria. Riboflavin (B2) supports flavin enzymes of the respiratory chain; niacin (B3) is used to make NADH; pantothenic acid (B5) to form coenzyme A. Thiamine (B1) is essential to enzyme complexes of the Krebs cycle, and iron forms part of complex I's eight iron–sulphur centres.
Exact wording: “Riboflavin contributes to normal energy-yielding metabolism”, “Niacin contributes to normal energy-yielding metabolism” and “Magnesium contributes to normal energy-yielding metabolism”. See our articles on vitamin B3 and forms of magnesium. Coenzyme Q10, L-carnitine and alpha-lipoic acid have no authorised health claim.
NAD+ precursors remain a research topic. In a 2020 trial of 40 men with obesity and insulin resistance, 2 g per day of nicotinamide riboside for 12 weeks, compared with a placebo, changed neither muscle NAD+ nor its mitochondria's respiration, quantity or shape. Other trials are covered in our NMN or NR comparison.
Frequently asked questions
Does a mitochondrion have a nucleus?
No. Its DNA is compacted into small packages, nucleoids, most often containing a single copy of the mitochondrial genome.
Why is a mitochondrion described as semi-autonomous?
Because it has its own DNA but makes only a tiny fraction of its proteins. During evolution, it transferred up to 99% of its genes to the nucleus: most of its proteins are produced in the cytoplasm and then imported.
Do all our cells have mitochondria?
Almost all. Red blood cells are an exception: as they mature, they lose their nucleus and eliminate their mitochondria through mitophagy, thanks to a protein called NIX.
Does mitochondrial DNA always come from the mother?
Almost always. A case of paternal origin was described in 2002 in the muscle of a patient with myopathy, but not in other patients subsequently studied. This inheritance remains exceptional and debated.
Can you measure the state of your mitochondria?
Not simply. The trials cited here analyse mitochondria obtained through muscle biopsy. Mitochondrial DNA copy number, sometimes measured in blood, differs between tissues, often without a relationship within the same person. It therefore does not necessarily tell us about other tissues.
Could persistent fatigue come from a mitochondrial disease?
It is possible, but unlikely: these genetic diseases are rare. Lasting fatigue has many other causes. If it persists for more than a few weeks, consult a doctor.
Conclusion
A mitochondrion is much more than a powerhouse: it makes most ATP, but also manages calcium, cell death, heat and certain hormones. Its capacity declines with age, partly because of inactivity. Endurance and interval training remain the best-demonstrated approaches, including after age 65.
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Food supplements do not replace a varied, balanced diet or a healthy lifestyle. Ask a healthcare professional for advice if you are taking medication, pregnant or breastfeeding.
