Key takeaways
Endurance training reliably builds mitochondria, a finding that goes back to Holloszy's 1967 rat study
Training volume seems to drive mitochondrial content, while intensity drives mitochondrial function
In healthy people VO2max is mostly limited by oxygen delivery, so mitochondria matter more for endurance than for the VO2max number
Mitochondria are the small structures inside muscle cells that use oxygen to turn fat and carbohydrate into usable energy. They are the last link in the oxygen chain: lungs, blood, heart, capillaries, muscle, mitochondria. So it is natural to assume that more mitochondria means a higher VO2max. The real picture is more interesting.
The discovery: training builds mitochondria
In 1967 John Holloszy trained rats on treadmills and measured the oxygen-using capacity of mitochondria in their leg muscles. Trained muscle had substantially more mitochondrial enzyme activity and a greater capacity to use oxygen than untrained muscle. This paper, published in the Journal of Biological Chemistry, founded the field of exercise biochemistry and is still cited as the moment we learned that muscle remodels itself in response to endurance work.
Later human studies confirmed it. In a classic eight-week cycling study, Andersen and Henriksson found about a 40% rise in key mitochondrial enzymes, a 20% rise in capillary density, and a 16% rise in VO2max. Notice the gap: the mitochondrial change was much larger than the VO2max change.
Mitochondrial biogenesis and PGC-1α
Mitochondrial biogenesis is the process of building new mitochondrial material. Each training session triggers signals inside the muscle fibre: calcium release, falling energy levels (sensed by an enzyme called AMPK), and mechanical and metabolic stress. These converge on a protein called PGC-1α, often described as the master regulator of mitochondrial biogenesis. PGC-1α switches on genes that produce new mitochondrial proteins.
One session produces a short-lived signal; repeated sessions add up to measurable change over weeks. That is why the pattern of training across weeks matters more than any single workout.
Volume vs intensity: two different adaptations
Cesare Granata, David Bishop and colleagues ran a series of studies that separated how many mitochondria you have (content) from how well they work (respiratory function):
| Study | What they changed | What happened |
|---|---|---|
| Granata 2016, intensity | 4 weeks of sprint intervals vs 4-minute intervals vs steady riding | Mitochondrial respiration and PGC-1α rose only after sprint intervals; markers of content did not change in any group |
| Granata 2016, volume | Normal training, then 20 days of twice-daily sessions, then reduced training | Normal volume changed nothing; very high volume raised respiration and citrate synthase by about 40 to 50%; gains largely vanished after 2 weeks of reduced training |
| Granata 2018 review | Pooled human studies | Volume appears to drive mitochondrial content; relative intensity drives respiratory function |
The practical lesson: easy volume and hard sessions do different jobs. Volume grows the size of the mitochondrial pool, intensity sharpens its quality. The volume study also shows how quickly the gains fade, which matches what we see in detraining.
Central vs peripheral limits
If mitochondria can grow by 40% or more, why does VO2max rise much less? Because in healthy people doing whole-body exercise, VO2max is mostly limited centrally, by oxygen delivery. In their 2000 review, Bassett and Howley concluded that the training-induced rise in VO2max comes primarily from a higher maximal cardiac output, not from greater oxygen extraction in muscle. Muscle has a spare capacity to consume oxygen that the heart cannot fully supply when the whole body is working.
Peripheral factors, mitochondria and capillaries, still matter a great deal, just for a different outcome. Bassett and Howley noted that more mitochondrial enzymes improve endurance by increasing fat use and reducing lactate build-up at a given oxygen uptake. In other words, mitochondria raise your lactate threshold and the fraction of VO2max you can hold, rather than the ceiling itself. See what limits VO2max for the full oxygen chain.
How to increase mitochondria
A simple weekly structure that targets both content and function:
- Build volume first. Three to five easy to moderate sessions a week, accumulating time. Easy running, cycling, rowing or brisk walking all count. Find your easy range with the heart rate zone calculator.
- Add one or two hard sessions. Intervals such as the Norwegian 4×4 or short sprint intervals sharpen mitochondrial function and push VO2max.
- Keep it consistent. Gains reverse within weeks, so steady training beats occasional heroic blocks.
- Progress gradually. Raise weekly time by small steps and keep most of it easy, as in 80/20 training.
Zone 2 training is one good way to accumulate volume, but there is nothing magic about a single heart-rate band: total work over weeks is what drives mitochondrial content.
Can you increase mitochondria without exercise?
Supplements marketed as "mitochondria boosters" are popular, but none has been shown to reproduce the broad remodelling that training produces in human muscle: more mitochondrial protein, more capillaries, better fat use and a higher threshold, all at once. Exercise remains the only intervention with decades of consistent human evidence behind it. If you are curious about supplements with genuine performance data, such as caffeine and dietary nitrate, see supplements for VO2max, and keep in mind that they act on performance on the day, not on how many mitochondria you build. Sleep and adequate energy intake matter too, because adaptation happens during recovery, not during the session itself.
What this means for your VO2max
Building mitochondria will make you better at endurance: lower heart rate at the same pace, better fat use, and the ability to sustain harder efforts. To move the VO2max number itself, you also need adaptations in the heart and blood, which respond best to a mix of volume and high-intensity intervals. A 12-week plan to improve VO2max combines both. Track progress every 6 to 8 weeks with the VO2max calculator.
Frequently asked questions
Do mitochondria increase VO2max?
Only a little. In healthy people doing whole-body exercise, VO2max is mostly limited by how much oxygen the heart and blood can deliver. More mitochondria mainly let you sustain a higher fraction of your VO2max for longer.
How do you increase mitochondria naturally?
Regular endurance exercise is the most reliable way. Accumulated volume, such as several easy to moderate sessions a week, raises mitochondrial content, and hard intervals add improvements in how well each mitochondrion works.
Does zone 2 training increase mitochondria?
Yes, easy aerobic training increases mitochondrial content, mostly through the total volume you accumulate over weeks. Zone 2 is not uniquely special though: harder training also builds mitochondria, and the two work well together.
How fast do you lose mitochondria when you stop training?
Quickly. In one study, gains from a very high-volume block had largely disappeared after only two weeks of reduced training, so consistency matters more than short bursts.
Sources
- Holloszy JO. Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem, 1967.
- Andersen P, Henriksson J. Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise. J Physiol, 1977.
- Bassett DR, Howley ET. Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med Sci Sports Exerc, 2000.
- Granata C, Oliveira RS, Little JP, Renner K, Bishop DJ. Training intensity modulates changes in PGC-1α and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle. FASEB J, 2016.
- Granata C, Oliveira RS, Little JP, Renner K, Bishop DJ. Mitochondrial adaptations to high-volume exercise training are rapidly reversed after a reduction in training volume in human skeletal muscle. FASEB J, 2016.
- Granata C, Jamnick NA, Bishop DJ. Training-induced changes in mitochondrial content and respiratory function in human skeletal muscle. Sports Med, 2018.