Mitochondrial Biogenesis: How Your Body Makes New Mitochondria

Key takeaways

• Mitochondrial biogenesis is how cells make new mitochondrial components, allowing existing mitochondria to grow and divide.

• PGC-1α is a key regulator that helps coordinate the genes involved in this process. Physical activity signals pathways involving this protein.

• Biogenesis builds mitochondrial material, while mitophagy removes damaged mitochondria. Both help maintain mitochondrial homeostasis, the balance of mitochondrial production and upkeep.

• A change in a signaling marker such as PGC-1α offers one piece of evidence. Additional measurements help clarify what that change means for mitochondrial biogenesis and everyday well-being.

• InfiniWell’s Cellular Energy Pro pairs liposomal NMN with urolithin A. Findings from studies on individual ingredients may not reflect how the combined formula affects mitochondrial biogenesis.

Mitochondria are structures inside cells that convert energy from food into adenosine triphosphate (ATP), a molecule that powers many cell activities. Through mitochondrial biogenesis, cells make the components needed for existing mitochondria to grow and divide, helping them meet the body’s energy needs.

If you’re reading about exercise, healthy aging, or supplements, understanding mitochondrial biogenesis can help you assess claims about mitochondrial health. This guide explains how the process works, how it differs from mitophagy, and what research says about everyday habits and supplements.

How do cells build new mitochondria?

Mitochondria sit inside cells, which supply most of the materials needed to build them. During mitochondrial biogenesis, cells make and assemble proteins, membranes, and copies of mitochondrial DNA (mtDNA) so existing mitochondria can grow and divide. This requires coordination between nuclear DNA, found in the cell’s nucleus, and the DNA inside mitochondria.

The process involves three tasks:

• Coordinating genetic instructions: Most mitochondrial proteins are made using instructions from nuclear genes, sections of DNA in the cell's nucleus. The mtDNA inside mitochondria carries instructions for a small number of proteins involved in ATP production.

• Protein production and delivery: Ribosomes, the cell’s protein-making structures, make most mitochondrial proteins outside the nucleus. Mitochondrial protein import machinery, groups of proteins that act as entry gates and guides, directs these proteins to their destinations, including the outer membrane, the inner mitochondrial membrane, and the matrix, the compartment enclosed by the inner membrane.

• Growth and assembly: Cells make membrane material, copy mtDNA, and assemble proteins into the structures needed for mitochondrial function. These steps allow existing mitochondria to grow and divide.

Researchers use different measurements to study these tasks, from gene activity to the production of mitochondrial proteins. Some measurements track signals that help start biogenesis, while others measure the production of new mitochondrial material.

For example, a change in PGC-1α alone shows a change in a protein that helps coordinate biogenesis, but it doesn’t confirm that the cell has built new mitochondrial components.

How does PGC-1α help coordinate biogenesis?

PGC-1α is a protein involved in regulating mitochondrial biogenesis. It helps coordinate genes needed to build mitochondria and support energy metabolism, particularly in tissues with high energy demands, such as skeletal muscle.

PGC-1α works as a coactivator. Rather than binding directly to DNA, it helps DNA-binding proteins called transcription factors direct gene activity. Several partners connect this process with the cell’s energy needs:

• NRF-1 and NRF-2 coordinate gene activity: These nuclear respiratory factors help activate genes involved in mitochondrial construction, including the gene for mitochondrial transcription factor A (TFAM).

• TFAM helps manage mitochondrial DNA: Once inside mitochondria, TFAM helps maintain mtDNA and supports its copying and reading. mtDNA transcription is the step that copies genetic instructions into ribonucleic acid (RNA), a molecule that helps cells use those instructions to make proteins. Together, PGC-1α, the nuclear respiratory factors, and TFAM help coordinate gene activity in the nucleus and mitochondria.

• AMPK senses energy availability: AMP-activated protein kinase (AMPK) responds when cellular energy availability falls. AMPK activation can lead to the addition of phosphate groups to PGC-1α, a process called phosphorylation that helps PGC-1α coordinate gene activity.

• SIRT1 modifies PGC-1α activity: SIRT1 is an enzyme that requires NAD+ to work. SIRT1 deacetylates PGC-1α, meaning it removes chemical tags called acetyl groups. This helps PGC-1α take a more active role in directing the genes involved in mitochondrial biogenesis.

Together, these proteins connect the cell’s energy needs with the genetic instructions required to build mitochondrial components.

What does human research show about mitochondrial biogenesis?

Researchers have examined how exercise and calorie restriction affect signals and measurements related to mitochondrial biogenesis. Exercise studies cover both the immediate response to a workout and adaptations after repeated training.

• Signals after one session: In a study of eight trained men, a single endurance exercise session resulted in more PGC-1α in muscle-cell nuclei, where it helps direct gene activity. This finding shows how muscle cells begin responding to the energy demands of exercise.

• Changes with repeated training: A separate two-week interval-training study reported changes in mitochondrial proteins and enzyme activity alongside changes in nuclear PGC-1α. These measurements help connect exercise signaling with adaptations in muscle tissue.

• Calorie restriction: Human studies have reported mixed findings. A six-month controlled study reported changes in mitochondrial DNA content and genes involved in biogenesis. In a separate 12-month trial, calorie restriction did not change the muscles’ maximum rate of ATP production or the activity of genes involved in biogenesis overall. These findings do not establish calorie restriction as a reliable way to promote mitochondrial biogenesis.

How does biogenesis differ from mitophagy, fusion, and fission?

Mitochondria form a network that changes as cells’ needs change. Four related processes help maintain this network:

Fusion and fission are called mitochondrial dynamics, the ongoing reshaping of the network. Together with biogenesis and mitophagy, they help cells maintain mitochondrial material and remove what's no longer needed.

For more on the cell’s recycling processes, see InfiniWell’s guide to autophagy and cellular health.

How can you support mitochondrial biogenesis day to day?

Regular physical activity is an excellent starting point, given the human research linking exercise with mitochondrial biogenesis. To build a routine you can maintain:

• Combine aerobic and strengthening activities: The Physical Activity Guidelines for Americans recommend both, adapted to your ability and health.

• Start at a manageable level: Choose activities you can repeat regularly, such as walking, cycling, or resistance exercises. Build up gradually as your fitness allows.

• Allow time between demanding sessions: Adjust the intensity and schedule so you can stay consistent without feeling pushed to do strenuous exercise every day.

• Support your routine with meals and sleep: Eat regularly and allow enough time for sleep to help sustain your activity habits. For practical bedtime tips, see our guide to deep sleep and healthy sleep habits. These habits support general well-being, though they don’t guarantee a specific change in mitochondrial biogenesis.

Understanding how your body builds mitochondria

Cells build mitochondrial material through a process called mitochondrial biogenesis. As energy needs change, biogenesis works alongside fusion, fission, and mitophagy to maintain the mitochondrial network.

Exercise research helps connect this biology to daily life. A single workout can trigger signals, while repeated training brings adaptations in muscle tissue.

For your everyday routine, start with manageable, regular physical activity. When considering supplements, check what researchers measured and whether they tested the finished formula or an individual ingredient.

Read InfiniWell’s guide to mitochondrial health supplements for a closer look at the research, or browse our healthy aging supplements collection to explore available options.