Mitophagy: What It Is, Mitophagy vs Autophagy and How to Support It

Mitophagy is the way your cells clear out worn, damaged mitochondria and recycle their parts, making room for healthy new ones. It is a targeted form of autophagy, the cell's wider recycling system. Healthy mitophagy is linked with healthy aging, and exercise and urolithin A are among the approaches that have been tested in people to support it.

Key Takeaways

• Mitochondria make most of the energy your cells run on. Mitophagy removes damaged ones and helps the cell build fully working replacements (Picca et al., 2023).
• Mitophagy is a selective type of autophagy: autophagy recycles many kinds of cell parts, while mitophagy targets mitochondria specifically (Killackey et al., 2020).
• Researchers link healthy mitophagy with healthy aging, and exercise and nutrition approaches that support it have now been tested in humans (Picca et al., 2023).
• Urolithin A is the best-studied nutrient for mitophagy: in human trials of 1 to 4 months it improved markers of mitochondrial health, and two trials found better muscle endurance or strength (Andreux et al., 2019; Singh et al., 2022).
• Spermidine supports autophagy, the broader recycling system that mitophagy is part of (Madeo et al., 2018).

What Is Mitophagy?

Mitochondria are the small structures inside your cells that turn food and oxygen into usable energy. Like any hard-working part, they wear out. Mitophagy (from "mitochondria" and the Greek for "eating") is the quality-control process that finds damaged mitochondria, wraps them up and sends them to the cell's recycling centers, the lysosomes, where they are broken down and their parts reused (Killackey et al., 2020).

Mitophagy does more than take out the trash. A 2023 review in Nature Metabolism describes how it also regulates the making of new, fully functional mitochondria, so the whole network stays healthy. The same review notes that mitophagy can now be measured in human blood, immune cells, muscle, brain and liver, and that impaired mitophagy is linked with poorer cellular health and with aging (Picca et al., 2023).

How Mitophagy Works

1. Spotting the damage. A mitochondrion that is working poorly gets flagged by tag proteins on its surface. The best-known signaling pair is PINK1 and Parkin, and cells have several other receptors and triggers too (Killackey et al., 2020).
2. Wrapping it up. The tagged mitochondrion is enclosed in a small membrane bubble.
3. Recycling. The bubble fuses with a lysosome, which breaks the mitochondrion down into building blocks the cell can reuse.
4. Renewal. The cell builds new mitochondria to replace the old ones, keeping energy production steady (Picca et al., 2023).

Mitophagy vs Autophagy

The two words are often used together, and they are related: mitophagy is one specific kind of autophagy.

	Autophagy	Mitophagy
What it recycles	Many kinds of worn cell parts and proteins	Mitochondria specifically
Main job	General cleanup and reuse of materials	Quality control of the cell's energy makers
Best-studied nutrient	Spermidine	Urolithin A
Lifestyle links	Fasting, exercise	Exercise

For the bigger picture of cellular recycling, including when it starts during fasting, read our guide to autophagy.

How to Support Mitophagy

Exercise

Exercise is one of the approaches the 2023 Nature Metabolism review lists among those already tested in humans for supporting mitophagy (Picca et al., 2023). Regular movement that challenges your muscles and your heart is a simple, free place to start.

Urolithin A

Urolithin A is a compound your gut bacteria make from ellagitannins in foods such as pomegranate, walnuts and berries. It was identified as a natural trigger of mitophagy: in worms it prevented the build-up of faulty mitochondria with age and extended lifespan, and in rodents it improved exercise capacity (Ryu et al., 2016). Human trials followed:

• First human trial. In healthy, sedentary older adults, 500 mg or 1,000 mg a day for 4 weeks was safe and changed markers of mitochondrial health in blood and muscle (Andreux et al., 2019).
• Adults aged 65 to 90. In 66 older adults, 1,000 mg a day for 4 months improved muscle endurance in hand and leg muscles and lowered blood markers linked to mitochondrial health and inflammation (Liu et al., 2022).
• Middle-aged adults. In 88 middle-aged adults, 500 mg or 1,000 mg a day for 4 months raised muscle strength by about 12 percent and improved aerobic endurance (Singh et al., 2022).

Not everyone's gut bacteria make much urolithin A from food, which is one reason people take it directly. Our guide to urolithin A benefits covers the trials, foods and safety in detail, and our urolithin A ingredient guide covers the compound itself.

Spermidine

Spermidine is a natural compound found in foods such as wheat germ, soybeans and mushrooms. It is one of the best-studied natural triggers of autophagy, the broader recycling system that mitophagy belongs to, and a review in Science describes its links with healthy aging in research models (Madeo et al., 2018). Read more in our guide to spermidine benefits and our spermidine ingredient guide.

Fasting and Daily Habits

Fasting is best known for switching on autophagy in general. Our guide to fasting and longevity explains what studies show and how to approach it safely. Good sleep and a varied, plant-rich diet support mitochondrial health too, and our cellular energy and mitochondrial health guide brings these habits together. Your gut bacteria make urolithin A from compounds in foods such as pomegranate and walnuts; see urolithin A foods. If you also take creatine, our guide to urolithin A and creatine compares what each one does and covers taking both.

Mitophagy and NAD+

Mitophagy and NAD+ both come up in conversations about mitochondria and aging, but they do different jobs. Mitophagy is about the quality of your mitochondria, clearing out worn ones. NAD+ is a molecule mitochondria use to turn food into energy, and its levels fall with age. Many people support both. See our guides to why NAD+ declines with age and how to increase NAD+ naturally. For how urolithin A and NMN fit together, see our guide to urolithin A vs NMN.

Where Our Products Fit

Our Urolithin A + Spermidine Capsules are built around the two sides of cellular recycling: urolithin A 500 mg, an amount used in the human trials, to support mitophagy, plus spermidine 6 mg from a gluten-free source to support autophagy, in every 2 capsules (planned formula). Many spermidine products are made from wheat germ; ours is planned from a gluten-free source. Every ingredient is third-party tested. They are coming soon, and you can join the waitlist on the product page.

If you want to support your mitochondria today, our Enhanced NMN capsules provide 750 mg of NMN, a building block of NAD+, plus resveratrol and pterostilbene per serving.

Frequently Asked Questions

What is mitophagy in simple terms?

It is your cells' way of clearing out worn or damaged mitochondria, the parts that make energy, and recycling them so healthy new ones can take their place.

What is the difference between mitophagy and autophagy?

Autophagy is the cell's general recycling system for many kinds of worn parts. Mitophagy is a selective type of autophagy that targets mitochondria only.

Why does mitophagy matter for aging?

Mitophagy keeps the mitochondrial network healthy. Researchers link impaired mitophagy with poorer cellular health and with aging, which is why ways to support it are being studied in people.

How can I support mitophagy naturally?

Regular exercise is the simplest place to start. Urolithin A is the best-studied nutrient for mitophagy, and spermidine supports autophagy more broadly.

What foods help mitophagy?

Pomegranate, walnuts and berries contain ellagitannins that some people's gut bacteria turn into urolithin A. Wheat germ, soybeans and mushrooms are rich in spermidine.

Does fasting trigger mitophagy?

Fasting is best known for switching on autophagy in general. See our autophagy and fasting guides for what studies show.

How long does urolithin A take to work?

Human trials measured changes after 1 to 4 months of daily use, with muscle findings at 2 to 4 months.

Is urolithin A safe?

In human trials of up to 4 months it was well tolerated, with no difference in side effects between urolithin A and placebo. Check with your clinician first if you are pregnant, breastfeeding or take prescription medication.

Sources

• Picca A, Faitg J, Auwerx J, Ferrucci L, D'Amico D. Mitophagy in human health, ageing and disease. Nature Metabolism, 2023. https://pubmed.ncbi.nlm.nih.gov/38036770/
• Killackey SA, Philpott DJ, Girardin SE. Mitophagy pathways in health and disease. Journal of Cell Biology, 2020. https://pubmed.ncbi.nlm.nih.gov/32926082/
• Ryu D, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine, 2016. https://doi.org/10.1038/nm.4132
• Andreux PA, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism, 2019. https://doi.org/10.1038/s42255-019-0073-4
• Liu S, et al. Effect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults: a randomized clinical trial. JAMA Network Open, 2022. https://doi.org/10.1001/jamanetworkopen.2021.44279
• Singh A, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicine, 2022. https://doi.org/10.1016/j.xcrm.2022.100633
• Madeo F, et al. Spermidine in health and disease. Science, 2018. https://doi.org/10.1126/science.aan2788

These statements have not been evaluated by the Food and Drug Administration. This content is for education and is not medical advice. Our products are not intended to diagnose, treat, cure or prevent any disease. Talk with a healthcare provider before starting a new supplement if you are pregnant, breastfeeding or taking medication.