Role of Mitochondria in Testosterone Production and Energy Metabolism

Mitochondria are often called the "powerhouses" of the cell, and for good reason. These tiny structures help produce most of the energy your bodies need to function.

However, did you know mitochondria also help in hormone production, including testosterone? Emerging research shows that the health of mitochondria is intricately connected to testosterone production and energy metabolism.

Want to know how? This article will help you explore the role of mitochondria in testosterone production, how they regulate energy metabolism, and much more.

What Are Mitochondria?

Mitochondria are small, double-membraned organelles found in almost every cell in the body. They have their own DNA (mtDNA) and are inherited primarily from the mother.

These organelles are best known for producing adenosine triphosphate (ATP) - the energy currency of the cell - through a process called cellular respiration.

However, mitochondria do more than just generate energy. They also:

• Regulate cell death (apoptosis)
• Manage calcium signaling
• Produce reactive oxygen species (ROS)
• Help synthesize certain hormones, including testosterone

What Is Testosterone and Why Is It Important?

Testosterone is a steroid hormone primarily produced in the testes in males and smaller amounts in the ovaries of females.

It plays a crucial role in a wide range of bodily functions, including sexual development and reproductive function, muscle and bone growth, mood and cognitive function, red blood cell production, and fat distribution and metabolism.

In males, testosterone is produced mainly by Leydig cells, which are found in the testes. The synthesis of testosterone is a complex process that starts with cholesterol and involves multiple steps and enzymes, many of which depend on mitochondrial activity.

How Is Testosterone Produced? The Basics of Steroidogenesis

The process to make steroid hormones, such as testosterone, is called steroidogenesis. It begins with cholesterol, a type of fat molecule, being transported into the mitochondria.

Once inside, it undergoes a series of chemical reactions to become pregnenolone, the first steroid in the pathway. Pregnenolone is then converted into other hormones, eventually resulting in testosterone.

Here's a simplified overview of the process:

• Cholesterol is transported into mitochondria.
• Inside mitochondria, cholesterol is converted to pregnenolone by an enzyme called CYP11A1 (also known as P450scc).
• Pregnenolone leaves the mitochondria and is further processed into testosterone in the smooth endoplasmic reticulum.

This initial mitochondrial step - conversion of cholesterol to pregnenolone - is rate-limiting and mitochondria-dependent, making it the most critical part of the testosterone production process.

Role of Mitochondria in Testosterone Production and Synthesis

Now, let's dive deeper into how mitochondria support the production of testosterone, a process that starts with cholesterol and heavily depends on mitochondrial function.

Cholesterol Transport to Mitochondria

The first big step in testosterone production is getting cholesterol into the mitochondria. This is made possible by a special protein called StAR (Steroidogenic Acute Regulatory protein).

Consider StAR as a gatekeeper. It helps move cholesterol from the outer mitochondrial membrane to the inner membrane, where hormone production begins. Without enough StAR, cholesterol builds up outside the mitochondria and can't be used properly, causing testosterone production to drop.

Enzymatic Conversion (CYP11A1)

Once cholesterol is inside the mitochondria, it undergoes a chemical transformation. The enzyme responsible is CYP11A1 (also called the cholesterol side-chain cleavage enzyme).

This enzyme converts cholesterol into pregnenolone, the first building block in the chain of reactions that leads to testosterone. The step occurs in the inner mitochondrial membrane and requires additional proteins, such as adrenodoxin and adrenodoxin reductase, which help transfer electrons needed for the reaction.  

Mitochondrial Health and Function

For this to work smoothly, the mitochondria must be healthy and efficient. If they are damaged due to aging, oxidative stress, poor diet, or toxins, the following things may happen:

• Cholesterol transport slows down
• Enzyme activity becomes less effective
• Energy (ATP) production drops

This often leads to lower testosterone levels. That's why it's essential to maintain strong, healthy mitochondria - not only for energy but also for hormonal health.When mitochondria function properly, testosterone synthesis is more efficient, supporting better physical performance, mood, and reproductive health.

If you believe you have low testosterone levels, Male Excel provides testosterone therapy (TRT) to help restore healthy levels and give you the confidence you need.

Mitochondria and Energy Metabolism: The ATP Factory

Apart from hormone production, mitochondria are best known for their role in energy metabolism. Here's how they do it:

Cellular Respiration and ATP Production

Mitochondria convert nutrients like glucose, fatty acids, and amino acids into ATP through a process known as oxidative phosphorylation.

This happens in numerous steps, including:

• Glycolysis (in the cytoplasm) breaks down glucose into pyruvate.
• Pyruvate enters the mitochondria and is converted into acetyl-CoA.
• Acetyl-CoA enters the Krebs cycle (also called the citric acid cycle).
• Electrons generated in the Krebs cycle are sent to the electron transport chain (ETC).
• The ETC produces a proton gradient that drives the production of ATP via ATP synthase.

This process is highly efficient and produces 30-32 molecules of ATP per glucose molecule.

Metabolic Flexibility

Healthy mitochondria can switch between different fuel sources depending on what's available, like glucose, fats, or ketones. This flexibility ensures that the body has a continuous energy supply.

Mitochondria in Muscle and Brain Cells

Muscle and brain tissues have high energy demands and contain many mitochondria. Efficient mitochondrial energy production supports:

• Muscle strength and endurance
• Mental clarity and mood
• Thermoregulation and metabolism

Factors That Harm Mitochondria (and Lower Testosterone)

Many lifestyle and environmental factors can damage mitochondria and reduce testosterone levels, such as:

• Poor Diet: A diet high in sugar, processed foods, and trans fats leads to inflammation and oxidative stress, two major enemies of mitochondrial health. Without the right nutrients, mitochondria can't function properly, and testosterone levels often decline as a result.
  
• Chronic Stress: Stress causes the body to release a hormone called cortisol. While cortisol is helpful in short bursts, constantly high levels can interfere with testosterone production. High cortisol also damages mitochondria, which makes it harder for your cells to produce energy and hormones effectively.
  
• Toxins: Everyday chemicals like BPA (found in plastics), pesticides, and heavy metals (like lead or mercury) can directly harm mitochondria. These toxins create oxidative stress, damage mitochondrial DNA, and interrupt hormone production pathways, including those that produce testosterone.
  
• Lack of Sleep: Sleep is when your body repairs and restores itself. Poor or insufficient sleep disrupts mitochondrial repair and lowers testosterone levels, especially if it's a long-term problem.
  
• Sedentary Lifestyle: Physical activity boosts mitochondrial function and supports testosterone production. Sitting too much and not exercising weakens your mitochondria, which might lead to lower energy and hormone levels.
  
• Obesity and Insulin Resistance: Excess body fat, especially around the belly, releases harmful substances that damage mitochondria and reduce testosterone. Insulin resistance, often caused by poor diet and lack of activity, adds even more stress to the system.
  
• Aging: As you age, your mitochondria naturally decline in number and efficiency. This is one reason why testosterone levels often drop with age.

When these factors are left unchecked, they create a cycle of poor energy, declining mitochondrial function, and lower testosterone, impacting your health, mood, and performance.

How to Support Mitochondrial and Hormonal Health

Mitochondria and hormones work together to keep your body functioning smoothly. Think of mitochondria as your body's power plants and hormones as the messengers that tell your body what to do, when to do it, and how much to do.

When either system falls out of balance, it can impact everything from mood and energy levels to muscle mass and metabolism. That being said, here are some practical, science-backed strategies to improve mitochondrial health and boost testosterone naturally so you can feel your best:

Eat for Mitochondrial Fuel and Hormone Balance

Your diet plays a huge role in mitochondrial function and hormone production. You want to fuel your body with the nutrients it needs to perform mitochondrial respiration, steroid hormone synthesis (such as testosterone and estrogen), and maintain mitochondrial homeostasis.

Here's what to focus on:

• Healthy fats: Omega-3s from fish, flaxseeds, and walnuts help build hormone-producing structures and support mitochondrial membrane health.
• Proteins: Proteins supply amino acids like L-carnitine, which helps shuttle fats into mitochondria for energy.
• Antioxidants: Berries, leafy greens, and colorful vegetables help neutralize reactive oxygen species (ROS) and reduce oxidative damage to mitochondrial DNA and mitochondrial proteins.
• Micronutrients: Magnesium, zinc, selenium, and B vitamins are critical for hormone production, mitochondrial gene expression, and mitochondrial matrix enzyme activity.

Tip: Avoid processed foods, excess sugar, and trans fats, which promote inflammation and impair mitochondrial and hormonal function.

Exercise Regularly to Promote Mitochondrial Biogenesis

Exercise isn't only good for your muscles, it's also an effective way to promote mitochondrial biogenesis (the creation of new mitochondria) and improve testosterone levels.

It helps to:

• Boost mitochondrial mass and enhances mitochondrial complexes in skeletal muscle.
• Increase mitochondrial respiration and ATP production.
• Enhance insulin sensitivity, which helps balance hormones.
• Trigger the release of hormones like testosterone and growth hormone.

Both aerobic exercise (such as brisk walking or cycling) and resistance training (like weightlifting) stimulate mitochondrial dynamics, especially mitochondrial fission and fusion, helping your body get rid of defective mitochondria and generate new ones.

Even moderate daily movement makes a big difference, especially in aging populations where age-related mitochondrial dysfunction and hormone decline are common.

Prioritize Sleep and Stress Management

Poor sleep and chronic stress are two of the biggest enemies of mitochondrial and hormonal health. They disrupt gene expression, damage mitochondria, and lower sex hormone levels.

Here are a few ways sleep and stress can have an impact:

• Sleep deprivation reduces ATP production and impairs mitochondrial function.
• Chronic stress increases cortisol (a catabolic hormone) and reduces testosterone and estrogen.
• Elevated cortisol increases the production of reactive oxygen species, leading to oxidative damage to mitochondrial membranes and mitochondrial DNA.

Try relaxation practices such as meditation, deep breathing, or yoga. Also, aim for 7-9 hours of quality sleep to allow for mitochondrial repair and hormonal recalibration.

Support Hormone Levels Naturally

Both testosterone and estrogen are crucial to metabolic and mitochondrial health. Testosterone, in particular, helps improve motor function, supports mitochondrial localization, and maintains skeletal muscle mass.

Listed below are some actionable ways to support hormone production naturally:

• Maintain A Healthy Body Weight: Excess body fat can lead to testosterone deficiency and increase the conversion of testosterone to estrogen.
• Avoid Endocrine Disruptors: BPA, phthalates, and other chemicals in plastics and personal care products can interfere with hormone receptors and estrogen receptor β signaling.
• Eat Cruciferous Vegetables: Broccoli, kale, and Brussels sprouts help balance estrogen metabolism and protect against female brain aging and hormonal imbalances.

In cases of significant testosterone deficiency, especially in older men, doctors may consider exogenous testosterone supplementation or hormone replacement therapy. However, these should always be used with caution and under medical supervision, as they can affect mitochondrial gene expression and protein levels.

Use Supplements That Improve Mitochondrial Function

Supplements can help when diet and lifestyle changes aren't enough. Several nutrients support mitochondrial biogenesis, reduce oxidative stress, and help maintain mitochondrial homeostasis.

Here are a few supplements you may consider:

• CoQ10: Essential for the mitochondrial electron transport chain and ATP production.
• Alpha-lipoic acid: A powerful antioxidant that protects against oxidative damage and improves energy metabolism.
• Acetyl-L-carnitine: Supports fat metabolism in mitochondria and helps regenerate damaged mitochondria.
• Vitamin D: It helps in hormone regulation and mitochondrial gene transcription.
• Resveratrol: Activates mitochondrial transcription factor A (TFAM), which helps maintain the mitochondrial genome.

Before you start any supplements, it's best to talk with a healthcare provider and, if possible, run biochemical assays or tests to understand your current mitochondrial or hormonal status.

Reduce Mitochondrial Toxins and Risk Factors

Your environment and habits can either support or sabotage your mitochondria and hormones. Oxidative phosphorylation is a delicate process, and even small disruptions can lead to long-term damage.

Make sure to limit or avoid:

• Smoking and Excess Alcohol: Both increase oxidative damage and impair mitochondrial membrane potential.
• Environmental Toxins: Pesticides, heavy metals, and air pollution affect nuclear and mitochondrial genomes, reducing mitochondrial gene expression.
• Sedentary Lifestyle: Lack of movement promotes mitochondrial dysfunction and reduces hormone production.

Monitor Changes with Age

As you age, there is a natural age-related decline in mitochondrial ATP production and hormone output. Normal aging can cause decreased expression of mitochondrial genes, loss of mitochondrial content, and reduced responsiveness to sex hormones.

For both men and women:

• Brain testosterone deficiency leads to cognitive changes and may contribute to neurodegenerative diseases.
• Hormonal imbalances can change how estrogen regulates oxidative metabolism in various brain regions.
• Women may see shifts in mitochondrial function during menopause due to dropping estrogen levels.

When you understand these patterns, they can help you take proactive steps to slow decline and support long-term health.

Conclusion

There you have it! Now you know mitochondria not only power your cells but are also essential for hormone production, especially testosterone. From converting cholesterol into pregnenolone to supplying energy for the whole process, this organelle is at the heart of both hormone balance and energy metabolism.

If you're struggling with low energy, poor recovery, brain fog, or signs of low testosterone, it may be time to focus on your mitochondrial health. Support your mitochondria with a nutrient-rich diet, regular exercise, quality sleep, and stress management.

Remember, when you take care of your mitochondria, it can help you feel more energized, focused, and hormonally balanced - no matter your age.

References

1.  Author links open overlay panelLucía Pronsato, 2, H. induces N. and, AbstractThe reduction in muscle mass and strength with age, Alexaki, V., Bradford, M. M., Cammarata, P., Chen, H., Chen, J. Q., Clayton, D. A., Dairaghi, D. J., Demonacos, C., Dupont-Versteegden, E. E., Evans, M. J., Frezza, C., Garesse, R., Giulietti, A., Griparic, L., He, B., Hofer, T., … Chen, J. (2019, October 30). Testosterone induces up-regulation of mitochondrial gene expression in murine C2C12 skeletal muscle cells, accompanied by an increase of nuclear respiratory factor-1 and its downstream effectors. Molecular and Cellular Endocrinology. https://www.sciencedirect.com/science/article/abs/pii/S0303720719303338#preview-section-cited-by

2.  Rojas-Zambrano, J. G., Rojas-Zambrano, A. R., Rojas-Zambrano, A. F., & Barahona-Cueva, G. E. (2025). Benefits of Testosterone Hormone in the Human Body: A Systematic Review. Cureus, 17(2), e78785. https://doi.org/10.7759/cureus.78785

3.  Bracci, M., Zingaretti, L., Martelli, M., Lazzarini, R., Salvio, G., Amati, M., Milinkovic, M., Ulissi, A., Medori, A. R., Vitale, E., Ledda, C., & Santarelli, L. (2023). Alterations in Pregnenolone and Testosterone Levels in Male Shift Workers. International journal of environmental research and public health, 20(4), 3195. https://doi.org/10.3390/ijerph20043195

4.  Leproult, R., & Van Cauter, E. (2011). Effect of 1 week of sleep restriction on testosterone levels in young healthy men. JAMA, 305(21), 2173-2174. https://doi.org/10.1001/jama.2011.710

5.  Herbst, E. A., Paglialunga, S., Gerling, C., Whitfield, J., Mukai, K., Chabowski, A., Heigenhauser, G. J., Spriet, L. L., & Holloway, G. P. (2014). Omega-3 supplementation alters mitochondrial membrane composition and respiration kinetics in human skeletal muscle. The Journal of physiology, 592(6), 1341-1352. https://doi.org/10.1113/jphysiol.2013.267336

6.  Khan, S. U., Jannat, S., Shaukat, H., Unab, S., Tanzeela, Akram, M., Khan Khattak, M. N., Soto, M. V., Khan, M. F., Ali, A., & Rizvi, S. S. R. (2023). Stress Induced Cortisol Release Depresses The Secretion of Testosterone in Patients With Type 2 Diabetes Mellitus. Clinical medicine insights. Endocrinology and diabetes, 16, 11795514221145841. https://doi.org/10.1177/11795514221145841

Share

• 
• 
• 

Tags

Health