What Is Mitochondrial Biogenesis?

Reviewed by SOMA HEALTH's Medical Research Team

Mitochondrial biogenesis is the process your cells use to build new mitochondria and expand their existing network. It is one half of a constant renewal cycle: old, worn components are cleared away while fresh capacity is added. Understanding how that cycle works helps explain why exercise is so powerful, and where a compound like urolithin A is being studied.

What mitochondrial biogenesis actually means

Mitochondria are the organelles that convert nutrients and oxygen into ATP, the chemical energy that powers nearly everything your cells do. They are not fixed in number. Cells continuously remodel their mitochondrial network to match demand, and mitochondrial biogenesis is the growth side of that remodeling: the coordinated production of new mitochondrial proteins, membranes, and copies of mitochondrial DNA that allow existing mitochondria to grow and divide.

The word biogenesis simply means the making of something new. In this context it does not mean mitochondria appear from nothing. New mitochondria arise from existing ones, expanding the network so a cell can generate more energy, buffer more oxidative stress, and support more activity. Tissues with high energy needs, such as skeletal muscle, heart, and brain, carry the densest mitochondrial populations and depend most on keeping that network healthy.

Biogenesis is only half the story

Building new mitochondria is only useful if damaged ones are also removed. That removal process is called mitophagy, a targeted form of cellular recycling in which the cell tags a worn-out mitochondrion and breaks it down for parts. Biogenesis and mitophagy work as a pair. When both run well, the network stays efficient. When mitophagy slows, damaged mitochondria accumulate and the average quality of the network drops even if the total number stays the same. You can read more in our explainers on what mitophagy is and on mitochondrial health.

The molecular switch: PGC-1α and its partners

At the center of mitochondrial biogenesis sits a protein called PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha). It acts as a master coactivator, meaning it does not build mitochondria itself but switches on a broad program of genes that do. When PGC-1α is activated, it works with transcription factors such as NRF-1 and NRF-2 to drive expression of nuclear genes for mitochondrial proteins, and with TFAM to promote replication of mitochondrial DNA. Because most mitochondrial proteins are encoded in the cell nucleus, this cross-talk between the nucleus and the mitochondria has to be tightly coordinated.

Several upstream signals converge on this pathway. AMPK, an enzyme that senses low cellular energy, and SIRT1, a sensor tied to NAD+ availability, both feed into PGC-1α activity. This is why conditions that stress a cell's energy supply, most obviously exercise, are such strong triggers for building new mitochondria. Research in human muscle has shown that the molecular events of exercise-induced biogenesis can begin very early, even before large increases in PGC-1α protein are measurable, underscoring how layered the signaling really is.

What reliably drives biogenesis in humans

Endurance and interval exercise

The most established, human-proven trigger for mitochondrial biogenesis is aerobic exercise. Repeated bouts of endurance or high-intensity interval training place recurring energy demand on muscle, activating AMPK and the PGC-1α program, and over weeks this increases mitochondrial density and oxidative capacity in trained muscle. This adaptation is a large part of why aerobic fitness improves with consistent training and why it tracks with markers like VO2 max.

Resistance training, heat, cold, and diet

Resistance training contributes too, primarily by adding muscle and supporting its energetic machinery. Other stressors studied in humans, including heat exposure, cold exposure, and dietary patterns that lower cellular energy availability such as fasting windows, can nudge the same pathways, though the size and consistency of these effects vary. Across all of them the theme is the same: a manageable, repeated stress signals the cell that it needs more capacity, and the cell responds by building.

Where urolithin A fits in

Urolithin A is a compound your gut bacteria can produce from ellagitannins, the polyphenols found in pomegranates, walnuts, and some berries. Not everyone's microbiome makes it efficiently, which is one reason direct supplementation has been studied. Importantly, urolithin A is best characterized as a driver of mitophagy, the recycling side of the cycle, rather than as a classic biogenesis stimulant. The two processes are complementary: clearing damaged mitochondria helps the surviving network run more cleanly.

The human evidence to date centers on mitochondrial and muscle-related outcomes. A first-in-human trial by Andreux and colleagues (2019, Nature Metabolism) reported that urolithin A was safe and well tolerated at doses up to 1,000 mg per day and shifted a mitochondrial gene-expression signature in older adults. Singh and colleagues (2022, Cell Reports Medicine) studied 500 mg and 1,000 mg daily over four months in middle-aged adults and reported effects on muscle strength and aspects of exercise performance. Liu, D'Amico and colleagues (2022, JAMA Network Open) reported improvements in muscle endurance in older adults over roughly four months. A 2025 randomized trial in Nature Aging reported support for immune-cell mitochondrial health in midlife adults over about 28 days.

The preclinical picture is broader but should be read as earlier-stage. Ryu and colleagues (2016, Nature Medicine) showed in cells and animals that urolithin A induced mitophagy, extended lifespan in the worm C. elegans, and improved muscle measures in rodents. That work motivated the human trials but does not, on its own, establish outcomes in people. For a fuller walk-through of the trials, see our urolithin A clinical studies summary and the broader urolithin A guide.

Honest limitations

A few things are worth holding in mind. First, human urolithin A research is still emerging; a 2024 systematic review in Ageing Research Reviews concluded exactly that. Second, most of the strongest human data concern muscle and mitochondrial gene-expression markers rather than the number of new mitochondria built. Third, individual response varies, partly because of differences in the gut microbiome. Supplements support normal physiology; they do not replace training, sleep, or a sensible diet, and they are not treatments for any medical condition. If you have a health concern or a diagnosed condition affecting your energy or muscles, talk with your doctor before adding anything new.

How to support the whole cycle

The practical formula is unglamorous but consistent with the evidence. Move regularly, mixing aerobic work with resistance training to signal for both capacity and strength. Prioritize sleep and protein, which supply the raw materials and recovery windows your cells need. Consider whether your diet includes the polyphenol-rich foods that feed urolithin A production; our page on foods high in urolithin A covers the sources. And if you choose a supplement, treat it as one input among many rather than a shortcut. If you are comparing formats and brands, our roundup of the best urolithin A gummies lays out what to look for.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This guide is educational and is not a substitute for advice from a qualified healthcare provider.