Everything You Need to Know About Your Mitochondria

You have probably heard mitochondria described as “the powerhouse of the cell.” It is one of those phrases most of us vaguely remember from high-school biology and then promptly forgot. But while the description is not wrong, it massively undersells what mitochondria actually do.

Mitochondria are microscopic structures found throughout most of the cells in your body. Their best-known role is helping convert energy from the nutrients you consume into adenosine triphosphate, or ATP, a form of chemical energy your cells can actually use. But energy production is only the beginning. Mitochondria are also involved in metabolism, cellular signalling, calcium regulation, responses to cellular stress and programmed cell death. They are constantly being remodelled, repaired, recycled and replaced as your cells adapt to the demands placed upon them.

They also possess something particularly unusual: mitochondria have their own DNA.

Your muscles depend on them. Your brain depends on them. Your heart is packed with them. Every time you move, think, train, recover or simply get through another day, an enormous mitochondrial network is quietly helping your cells meet their changing energy requirements.

So perhaps “powerhouse of the cell” is not wrong. It is just nowhere near the whole story.

Mitochondria are specialised structures called organelles that live inside most human cells. Different cell types contain different amounts of mitochondrial machinery depending largely on their function and energy requirements. The heart provides an obvious example. Cardiac muscle must contract continuously, every minute of every day, which creates an extraordinary and relentless demand for ATP.

Skeletal muscle is another good example, but for a different reason. Its energy requirements can change dramatically within seconds. Sitting on the couch requires one level of energy production. Sprinting up a hill requires something completely different. Your muscle cells therefore need an energy system capable not only of generating energy, but of repeatedly responding to changing demand.

The brain, liver and kidneys are also highly metabolically active tissues with substantial mitochondrial requirements. But mitochondria are not simply identical little batteries floating independently inside these cells. They form a dynamic system capable of changing according to the condition and requirements of the cell.

Their story becomes even stranger when we look at where they came from.

Mitochondria retain their own genetic material, known as mitochondrial DNA, or mtDNA. Human mitochondrial DNA is a small circular genome containing 37 genes. Most of the proteins required to build and maintain mitochondria are encoded by DNA inside the cell nucleus, but mitochondria have retained this small genetic system of their own.

The leading explanation comes from one of the most remarkable events in evolutionary biology. More than a billion years ago, an ancestral cell is believed to have incorporated a bacterium capable of efficiently using oxygen in energy metabolism. Instead of simply being destroyed, that bacterium persisted. Over an immense period of evolutionary time, the relationship became increasingly integrated until the once-independent organism eventually became what we now recognise as the mitochondrion.

This idea is known as the endosymbiotic theory, and it helps explain several unusual mitochondrial characteristics, including their double membrane and circular DNA.

So hidden inside almost every cell in your body is the evolutionary descendant of something that, an unimaginably long time ago, existed far more independently.

That is pretty remarkable when you stop and think about it.

To understand why mitochondria matter so much, it helps to understand ATP.

ATP stands for adenosine triphosphate, and it is commonly described as the energy currency of the cell. That is actually a useful analogy. The food you eat contains chemical energy, but your cells cannot simply throw a piece of chicken, rice or stored body fat at a contracting muscle fibre and tell it to get to work.

Those nutrients first need to be processed through interconnected metabolic pathways. Carbohydrates can provide glucose, fats provide fatty acids and proteins provide amino acids. Energy can ultimately be extracted from these fuels, with mitochondria playing a central role in capturing much of that energy in ATP.

ATP can then power an extraordinary range of cellular processes. Muscle contraction requires it. Maintaining ion gradients across cell membranes requires it. Cellular transport requires energy. Building molecules and maintaining tissues requires energy. The countless chemical reactions necessary for life depend directly or indirectly on a continual supply of usable energy.

And continual is the important word.

Your body does not maintain a giant warehouse containing months' worth of ATP. ATP is constantly being consumed and regenerated, every second, every minute, every day, for your entire life.

A mitochondrion has both an outer membrane and a highly specialised inner membrane. The inner membrane folds inward into structures called cristae, greatly increasing the available surface area for the molecular machinery involved in energy production.

Embedded within this membrane is the electron transport chain. Electrons derived ultimately from the nutrients you consume are passed through a series of protein complexes. As those electrons move through the system, their energy helps pump protons across the inner mitochondrial membrane. This creates an electrochemical gradient, essentially stored potential energy across the membrane.

Then comes one of biology's most extraordinary molecular machines: ATP synthase.

Protons flow back across the membrane through ATP synthase, and the energy associated with that movement helps drive the formation of ATP. The overall process is known as oxidative phosphorylation.

There is an enormous amount of chemistry hidden inside that explanation, but the central idea is simple enough. Your mitochondria create a controlled electrochemical system that helps transform energy obtained from nutrients into a form your cells can actually spend.

And they perform this process continuously on an extraordinary scale.

Yet describing mitochondria purely in terms of ATP production still leaves out one of their most important characteristics.

Mitochondria are not static.

They can grow, divide, join together, separate and reorganise themselves. Damaged sections can be isolated. Components can be broken down and recycled. New mitochondrial material can be produced. Rather than imagining hundreds of identical batteries floating independently around a cell, it is more accurate to imagine a dynamic network constantly adjusting itself to cellular conditions.

Two processes central to this behaviour are known as fusion and fission.

During mitochondrial fusion, mitochondria join and exchange contents. This allows components to mix throughout the mitochondrial network and can help support its overall function. Fission essentially does the opposite: a mitochondrion divides.

Fission performs several normal functions, including helping distribute mitochondria, but it can also help separate dysfunctional portions of the mitochondrial network from healthier material. Once damaged material has been isolated, another process becomes extremely important: mitophagy.

Mitophagy is the selective removal of mitochondria through the cell's broader autophagy machinery. When mitochondria become sufficiently damaged or dysfunctional, cellular quality-control pathways can target that material for degradation and recycling.

Think of it like maintaining a fleet of vehicles. Continually purchasing more vehicles while refusing to service, repair or retire damaged ones would eventually leave you with an enormous fleet that functions terribly.

Your cells face a similar problem.

This is why mitochondrial health is not simply about how many mitochondria you have. Quality matters just as much as quantity.

More is not automatically better.

Another concept that appears constantly in mitochondrial biology is reactive oxygen species, or ROS. You may have heard them discussed under the broader label of free radicals, usually accompanied by the very simple idea that free radicals are bad and antioxidants are good.

Real biology is considerably more complicated.

Reactive oxygen species can be generated during cellular metabolism, and excessive oxidative stress can damage proteins, lipids, DNA and other cellular structures. But ROS are not simply metabolic rubbish. They can also act as signalling molecules.

Small and controlled changes in reactive oxygen species help cells recognise and respond to stress. Exercise provides a perfect example. During physical activity, energy demand changes dramatically. Calcium signalling changes. Cellular energy status changes. Redox signalling changes.

Those temporary disturbances contribute to the signals telling the cell that something has happened and adaptation may be required.

The goal therefore is not necessarily to eliminate every reactive molecule inside the body. It is to maintain appropriate redox balance while preserving the signalling required for normal cellular function and adaptation.

Your body was not designed to exist in an environment containing absolutely no biological stress. In many circumstances, a manageable challenge is precisely what stimulates adaptation.

Like almost every biological system, mitochondria are not immune to damage or dysfunction. Changes can occur in ATP production, electron transport, mitochondrial membrane potential, oxidative balance, mitochondrial DNA, fusion and fission, mitophagy, biogenesis and metabolic signalling.

Importantly, mitochondrial dysfunction is not one single disease or one single biological defect. It is an umbrella term that can describe disruptions across an extremely complicated system.

Altered mitochondrial function has been studied across ageing and numerous diseases, but this needs to be interpreted carefully. Finding mitochondrial dysfunction in a particular condition does not automatically prove that dysfunctional mitochondria caused that condition in the first place.

Sometimes mitochondrial dysfunction may contribute to disease. Sometimes it may arise as a consequence. In many situations, the relationship may work in both directions.

This distinction matters because mitochondrial science has increasingly entered the longevity and wellness world, where complicated findings can quickly become simplified into claims such as “mitochondrial dysfunction causes ageing”.

Reality is not that neat.

Ageing involves interconnected changes across virtually every biological system. Mitochondria are an important part of that picture, but they do not operate independently of everything else happening inside the body.

What researchers are increasingly interested in is mitochondrial resilience. Can cells continue producing energy appropriately? Can mitochondria respond when energy demand changes? Can damaged components be recognised and removed? Can the network rebuild and remodel itself? Can it maintain the flexibility required to respond to physiological stress?

Those questions bring us to mitochondrial biogenesis.

Mitochondrial biogenesis broadly describes the coordinated process through which cells produce mitochondrial components and expand or renew mitochondrial capacity. This is more complicated than simply pressing a biological button labelled “make mitochondria”. Remember that mitochondria contain their own DNA while relying heavily on genes contained within the cell nucleus. Building and maintaining the mitochondrial network therefore requires coordination between these genetic systems.

One of the most extensively studied regulators involved in this process is PGC-1α, or peroxisome proliferator-activated receptor gamma coactivator 1-alpha.

Do not worry. There will not be a test.

PGC-1α helps coordinate gene-expression programs involved in oxidative metabolism and mitochondrial biogenesis. And one of the most powerful physiological stimuli capable of driving mitochondrial adaptation is something humans were doing long before we knew mitochondria existed.

Exercise.

Before supplements, peptides, longevity clinics and biohacking, there was movement.

Exercise remains one of the best-established ways of stimulating mitochondrial adaptation, particularly within skeletal muscle. When you exercise, your muscle cells suddenly face increased energy demand. ATP is consumed more rapidly. Calcium concentrations fluctuate. Cellular energy sensors recognise changes in metabolic status. Redox signalling changes.

In simplified terms, the cell receives a message: the current system has just been challenged, and we may need to be better prepared when this happens again.

When that challenge occurs repeatedly and adequate recovery follows, adaptation can occur.

Pathways involving molecules such as AMP-activated protein kinase, or AMPK, and PGC-1α help translate temporary metabolic stress into longer-term changes in cellular machinery. Repeated exercise can increase mitochondrial proteins, mitochondrial content and oxidative capacity within skeletal muscle.

But exercise does something more sophisticated than simply encouraging cells to build more mitochondria.

Training also interacts with the systems controlling mitochondrial quality. Exercise influences mitochondrial biogenesis, fusion, fission and mitophagy. In other words, the adaptation is not simply “make more mitochondria”.

It is part of a much broader process of mitochondrial remodelling.

Build. Repair. Reorganise. Recycle. Adapt.

Then do it again.

This distinction becomes particularly important when mitochondrial science enters the supplement and biohacking world.

A compound increases a marker associated with mitochondrial biogenesis and suddenly it is marketed as creating more mitochondria. Something increases ATP production in an experiment and now it is an energy booster. Something reduces a marker of oxidative stress and now it is protecting your cells from ageing.

But physiology rarely works in such simple straight lines.

A healthy mitochondrial system involves quantity, quality, efficiency, dynamics, quality control and adaptability. You need sufficient mitochondrial capacity to meet cellular energy demands. You need functioning machinery. You need mitochondrial networks capable of reorganising themselves. You need systems capable of recognising and clearing dysfunctional material. And you need the entire network to respond appropriately when the metabolic environment changes.

Mitochondria are not a battery percentage you simply want to push from 70% to 100%.

They are part of a living, responsive and constantly changing biological network.

And that is precisely why mitochondria have become such an exciting target for modern research.

Scientists are not only asking how mitochondria produce ATP anymore. They are asking whether mitochondrial membranes can be protected, whether mitochondrial signalling can be manipulated, whether cellular energy metabolism can be altered, whether mitochondrial quality control can be influenced, and whether molecules can be designed — or discovered within our own biology — that affect these processes directly.

Four areas of research provide a particularly interesting look at those questions: SS-31, MOTS-c, NAD+ and SLU-PP-332.

They do not do the same thing. They are not all peptides. And they are certainly not supported by the same level of evidence.

But together, they offer four very different windows into the future of mitochondrial research.

The first is SS-31, also known as elamipretide.

SS-31 is a small tetrapeptide developed around mitochondrial biology. Rather than simply encouraging cells to produce more mitochondria, it targets the inner mitochondrial membrane.

Within that membrane exists a particularly important phospholipid called cardiolipin. Cardiolipin contributes to mitochondrial membrane organisation and interacts with proteins involved in oxidative phosphorylation. In simple terms, it helps support the environment in which much of the machinery responsible for mitochondrial energy production operates.

Elamipretide interacts with cardiolipin-rich mitochondrial membranes. Research has linked this interaction with changes in membrane properties, cristae organisation, respiratory-chain function and mitochondrial bioenergetics.

This is important because SS-31 was once frequently described primarily as a mitochondrial antioxidant. The modern picture is considerably more sophisticated.

Rather than simply floating around scavenging reactive molecules, elamipretide appears to influence the physical and functional environment in which mitochondrial energy-producing machinery operates.

That makes SS-31 particularly interesting from the perspective of mitochondrial quality and bioenergetic function, rather than simply mitochondrial quantity.

It has also progressed substantially beyond laboratory and animal research.

A randomised study in older adults with impaired skeletal-muscle mitochondrial function found that a single dose of elamipretide increased a measure of maximal mitochondrial ATP production shortly after administration. Importantly, this did not translate into a significant improvement in the study's measure of muscle fatigue resistance.

That is a perfect example of why biomarkers and functional outcomes should be separated.

The mitochondrial measurement changed.

That does not automatically mean the person suddenly became stronger or more physically capable.

Elamipretide has also been investigated clinically in several disease settings. Then, in September 2025, mitochondrial-targeted medicine reached an important milestone when the United States FDA granted accelerated approval to elamipretide, marketed as Forzinity, for improving muscle strength in adults and children with Barth syndrome weighing at least 30 kilograms.

Barth syndrome is an ultra-rare genetic mitochondrial disease involving abnormal cardiolipin biology.

That approval is significant, but it needs to be interpreted correctly.

It does not mean SS-31 has been proven as a general anti-ageing therapy, athletic-performance enhancer or universal mitochondrial optimiser. It means a therapy built around mitochondrial cardiolipin biology progressed from mechanistic research into an approved clinical application for one very specific mitochondrial disease.

That is remarkable enough without exaggerating it.

If SS-31 is fascinating because it targets mitochondria, MOTS-c may be even stranger.

MOTS-c stands for Mitochondrial Open Reading Frame of the 12S rRNA-c. It is a short mitochondrial-derived peptide associated with genetic information contained within mitochondrial DNA.

For decades, mitochondria were largely discussed as cellular machinery receiving instructions from elsewhere. The discovery of mitochondrial-derived peptides helped reveal a much more interesting picture.

Mitochondrial genetic information may itself contribute to signalling systems capable of influencing cellular physiology.

MOTS-c has attracted particular attention for its relationship with metabolic regulation and cellular stress responses. One pathway that repeatedly appears in MOTS-c research is AMPK, the same cellular energy-sensing pathway we encountered when discussing exercise.

Experimental research has connected MOTS-c with glucose metabolism, metabolic homeostasis and cellular responses to energetic stress. Under metabolic stress, MOTS-c has also been observed experimentally to move into the cell nucleus, where it can influence nuclear gene expression.

This represents a form of mitochondrial-to-nuclear communication.

Instead of thinking about instructions travelling only from the nucleus toward the mitochondria, we now have evidence of mitochondrial-derived signals participating in communication back toward the nucleus.

Mitochondria are not simply receiving orders.

They may also be sending messages.

MOTS-c becomes particularly interesting when we bring exercise into the picture. Research published in Nature Communications found that exercise was associated with increased endogenous MOTS-c in human skeletal muscle and circulation. The same research reported that administering MOTS-c to mice improved physical performance across different ages.

That finding understandably generated enormous interest, but the distinction matters.

Researchers observed an endogenous MOTS-c response to exercise in humans.

The dramatic intervention experiments involving administration of MOTS-c were performed predominantly in mice.

Those are two different levels of evidence.

This means we should not jump from “MOTS-c participates in human exercise biology” to “administering MOTS-c has been proven to improve human exercise performance”.

It has not.

The research is fascinating precisely because it suggests mitochondria may not simply respond passively to exercise. They may participate in signalling the body's response to it.

But we are still learning the language.

Then there is NAD+, which is different again.

It is not a peptide. It is not an experimental molecule invented in a laboratory. And it certainly is not something your body only encounters when someone puts it into a supplement or an IV bag.

NAD+ is already fundamental to life.

NAD stands for nicotinamide adenine dinucleotide, and it exists in interconnected oxidised and reduced forms, most famously NAD+ and NADH. These molecules participate in redox reactions throughout cellular metabolism.

NAD+ can accept electrons and become NADH. NADH can then donate electrons into metabolic pathways connected with mitochondrial respiration. This cycling between oxidised and reduced forms makes the NAD system fundamental to cellular energy transfer.

But NAD+ does more than participate in energy metabolism. It is also used by enzymes involved in cellular signalling, DNA repair, stress responses and metabolic regulation.

Among the best known are sirtuins, a family of NAD+-dependent enzymes that have attracted considerable attention in ageing research.

This connection between NAD+, metabolism, mitochondria and ageing produced an obvious question: could increasing NAD+ improve health as we age?

And this is where the science and the marketing begin to separate.

Two statements can simultaneously be true.

NAD+ is absolutely essential to normal cellular biology.

And increasing NAD+ does not automatically mean a person becomes healthier, younger or more energetic.

Research into NAD metabolism helped drive enormous interest in NAD+ precursors such as nicotinamide riboside, or NR, and nicotinamide mononucleotide, or NMN, alongside direct NAD+ administration.

Human studies have demonstrated that NR and NMN can alter NAD-related biomarkers.

So biologically, something is happening.

But changing a biomarker is not the same thing as producing a meaningful health outcome.

A 2026 systematic review examining 113 eligible human and rodent intervention studies found that oral NR and NMN consistently demonstrated biochemical target engagement in humans, but effects on functional, metabolic, vascular and other health-related outcomes were inconsistent and often limited to particular endpoints.

Perhaps even more importantly, given the popularity of NAD+ injections and infusions, the review found no eligible clinical outcome trials evaluating intravenous or intramuscular NAD+ itself for anti-ageing or wellness indications.

That does not mean NAD+ is useless.

Far from it.

It means we need to separate three different questions.

Is NAD+ biologically important?

Absolutely.

Can NAD-related interventions change NAD biology?

Yes.

Has increasing NAD+ been conclusively demonstrated to produce broad anti-ageing, energy and wellness benefits in humans?

Not yet.

That distinction is exactly what responsible mitochondrial research should look like.

Finally, we arrive at perhaps the most experimental compound in this discussion:

SLU-PP-332.

One thing needs to be clear immediately. SLU-PP-332 is not a peptide.

It is a synthetic small molecule developed as a research tool targeting a group of nuclear receptors known as estrogen-related receptors, or ERRs.

Despite their name, these are not simply estrogen receptors. ERRα, ERRβ and ERRγ help regulate gene-expression programs associated with energy metabolism and mitochondrial function.

Researchers recognised that ERR signalling overlaps with aspects of the metabolic program activated during endurance exercise. That created an intriguing question.

Could a molecule activate part of the molecular machinery normally stimulated by exercise?

Enter SLU-PP-332.

SLU-PP-332 acts as an agonist of ERRα, ERRβ and ERRγ, with particularly strong activity involving ERRα. In skeletal-muscle cells, researchers reported increased mitochondrial respiration following exposure to the compound.

Then came the animal experiments.

When administered to mice, SLU-PP-332 increased oxidative skeletal-muscle characteristics and enhanced exercise endurance.

That research helped produce the irresistible description: exercise mimetic.

But that phrase needs context.

Exercise is not one molecular pathway. It is an enormous whole-body physiological event. Your cardiovascular system responds. Your lungs respond. Your skeletal muscles contract. Mechanical forces are generated. Blood flow changes. Hormonal and neurological signalling changes. Bone and connective tissue experience loading. Energy sensors respond. Gene expression changes.

SLU-PP-332 does not recreate all of that.

What it has demonstrated experimentally is the ability to activate specific transcriptional programs that overlap with aspects of the metabolic response to endurance exercise.

That is still remarkable.

But it is not exercise in a vial.

Perhaps the most scientifically interesting thing about SLU-PP-332 is not the idea of avoiding cardio. It is what the molecule can teach researchers about the machinery behind exercise adaptation.

If activating ERR pathways reproduces particular metabolic effects associated with exercise, scientists can begin separating which molecular signals contribute to which adaptations.

That knowledge could eventually become important in circumstances where normal physical activity is difficult or impossible.

But that is a future possibility.

The major findings currently associated with SLU-PP-332 remain predominantly preclinical. There is an enormous evidentiary gap between “this increased endurance in mice” and “this improves endurance in humans”.

Those statements are not interchangeable.

And this is where all four compounds become more interesting when viewed together.

SS-31 investigates whether targeting the environment of the mitochondrial inner membrane and cardiolipin-associated biology can influence mitochondrial structure and bioenergetic function.

MOTS-c investigates signalling associated with mitochondrial genetic information and how mitochondria may communicate metabolic stress to the rest of the cell.

NAD+ sits within the fundamental chemistry of cellular metabolism and asks what happens when a naturally occurring metabolic cofactor is manipulated.

SLU-PP-332 approaches mitochondria indirectly, activating nuclear receptors involved in transcriptional programs associated with oxidative metabolism.

One targets the membrane.

One emerges from mitochondrial genetic information.

One participates in cellular metabolism.

One alters signals controlling metabolic gene expression.

There is no single “mitochondrial pathway”. There is an interconnected network of membranes, genes, enzymes, metabolites, signalling molecules and quality-control systems operating continuously throughout the cell.

Which means there probably will never be one molecule that simply “fixes your mitochondria”.

This also brings us to perhaps the most important concept in this entire discussion.

Scientific discoveries usually do not begin with enormous clinical trials involving thousands of people. They begin much earlier.

A researcher may discover that manipulating a molecule changes mitochondrial respiration in cultured cells.

Interesting.

Researchers might then administer a compound to mice and observe improved endurance or altered metabolism.

More interesting.

Eventually, early human studies may examine safety, pharmacology or biomarkers. Later still, controlled clinical trials can investigate whether an intervention produces meaningful outcomes in people.

This creates a rough progression from mechanism, to cells, to animals, to human biomarkers, and finally to human clinical outcomes.

Each step tells us something different.

Problems begin when those steps are collapsed into one another.

A compound increases mitochondrial respiration in cultured muscle cells and suddenly it “boosts human energy”.

A mouse runs further after receiving an experimental compound and suddenly it “increases endurance”.

A supplement increases a blood biomarker and suddenly it “reverses ageing”.

These claims often begin with genuine science.

The conclusion has simply travelled much further than the evidence.

Mitochondrial research is particularly vulnerable because the terminology sounds incredibly compelling.

Cellular energy.

Mitochondrial optimisation.

Metabolic rejuvenation.

Exercise mimetic.

The better question is less exciting but much more useful:

What was actually demonstrated?

There is no single number that measures mitochondrial health. Your smartwatch cannot tell you that your mitochondria are operating at 82%, and mitochondrial health is not simply about maximising ATP production.

A healthy mitochondrial network requires enough capacity to meet cellular energy demands. It requires functioning machinery. It requires flexibility when energy demand changes. It requires appropriate redox signalling rather than uncontrolled oxidative stress. It requires effective fusion, fission and quality control. It requires removal and recycling of damaged components. And it requires the ability to undergo biogenesis and remodelling when repeated physiological demand makes adaptation necessary.

That last word may be the most useful of all.

Adaptation.

Your mitochondria should not simply operate at maximum output every second of every day.

They should respond appropriately to what the cell requires.

When demand increases, the system responds.

When demand decreases, it adjusts.

When components become damaged, they can be repaired or removed.

When repeated stress indicates that greater oxidative capacity is required, the network can remodel.

Mitochondrial health may therefore be better thought of as mitochondrial resilience.

Not simply the ability to produce energy.

The ability to respond.

And after discussing mitochondrial peptides, experimental small molecules and NAD+ biology, the most evidence-based conclusion may sound disappointingly old-fashioned.

Exercise remains one of the most powerful and best-established ways we know of stimulating mitochondrial adaptation in humans.

This does not make emerging mitochondrial research irrelevant.

Quite the opposite.

Exercise provides researchers with one of the best biological models available for understanding how mitochondrial adaptation works.

When skeletal muscle repeatedly encounters increased energy demand, numerous signalling pathways respond. Over time, training can increase mitochondrial content and oxidative capacity while influencing mitochondrial dynamics and quality control.

That means exercise does not simply create more mitochondria.

It helps remodel the mitochondrial system.

This is also why the idea of an exercise mimetic is scientifically interesting. Researchers are not necessarily trying to replace your morning run. They are attempting to identify the molecular instructions that tell tissues to adapt to exercise.

Understanding those instructions could eventually have therapeutic value, particularly in situations where normal physical activity is severely limited.

But that is very different from saying scientists have invented exercise in a pill.

We are not there.

The way scientists think about mitochondria has changed enormously.

They are not isolated organelles quietly burning fuel in the background.

They communicate with the nucleus.

They interact with other cellular structures.

They alter their morphology.

They participate in signalling.

They contain their own genome.

They contribute to the production of signalling molecules.

They monitor and respond to the energetic state of the cell.

And their function can change dramatically according to physiological demand.

That opens an enormous number of research questions.

Can mitochondrial membranes be therapeutically targeted? Can mitochondrial-derived signals be harnessed? Can dysfunctional mitochondrial quality control be restored? Can exercise-associated metabolic programs be activated selectively? Can therapies target particular mitochondrial defects without disrupting normal mitochondrial signalling?

We are only beginning to answer those questions.

And that is exactly why mitochondrial science deserves far more than the phrase “powerhouse of the cell”.

If there is one idea worth taking away from everything we have covered, it is this:

Your mitochondria are designed to adapt.

They respond when you move. They respond when energy demand changes. They communicate with the rest of the cell. They remodel themselves. They remove damaged components. They create new mitochondrial material. They participate in the continuous process through which your cells attempt to maintain balance in an environment that is constantly changing.

Modern research is beginning to understand how some of those processes might be deliberately influenced.

SS-31 shows what may be possible when researchers target mitochondrial membrane biology.

MOTS-c shows that mitochondrial genetics may contain signalling systems we are still learning to understand.

NAD+ demonstrates just how deeply mitochondrial function is integrated with fundamental cellular metabolism.

SLU-PP-332 demonstrates how experimental molecules can be used to interrogate genetic programs associated with oxidative metabolism and exercise adaptation.

None of them changes the fundamental lesson.

Mitochondrial health is not simply about creating more energy.

It is not about maximising ATP.

And it certainly is not about discovering one magic molecule capable of turning your cells into microscopic superchargers.

It is about capacity, quality, efficiency, communication, maintenance and adaptation.

More than a billion years after an ancient biological partnership helped give rise to the mitochondria living inside our cells today, scientists are still discovering just how deeply these tiny structures influence biology.

The powerhouse analogy got one thing right.

Mitochondria are extraordinarily important.

We just had no idea how extraordinary they really were.

References & Further Reading

1. Drake JC, Wilson RJ, Yan Z. Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle. FASEB Journal. 2016;30(1):13–22. DOI: 10.1096/fj.15-276337. PMID: 26370848.

2. Hood DA, Memme JM, Oliveira AN, Triolo M. Maintenance of skeletal muscle mitochondria in health, exercise, and aging. Annual Review of Physiology. 2019;81:19–41.

3. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021;22:119–141. DOI: 10.1038/s41580-020-00313-x. PMID: 33353981.

4. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. 2015;21(3):443–454. DOI: 10.1016/j.cmet.2015.02.009. PMID: 25738459.

5. Kim KH, Son JM, Benayoun BA, Lee C. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metabolism. 2018;28(3):516–524.e7. DOI: 10.1016/j.cmet.2018.06.008. PMID: 29983246.

6. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021;12:470. DOI: 10.1038/s41467-020-20790-0. PMID: 33473109.

7. Roshanravan B, Liu SZ, Ali AS, et al. In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial. PLOS ONE. 2021;16(7):e0253849. DOI: 10.1371/journal.pone.0253849. PMID: 34264994.

8. Chavez JD, Tang X, Campbell MD, et al. Mitochondrial protein interaction landscape of SS-31. Proceedings of the National Academy of Sciences. 2020;117(26):15363–15373. DOI: 10.1073/pnas.2002250117. PMID: 32554501.

9. Mitchell W, Ng EA, Tamucci JD, et al. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. Journal of Biological Chemistry. 2020. PMID: 32273339.

10. United States Food and Drug Administration. FDA Grants Accelerated Approval to First Treatment for Barth Syndrome. September 19, 2025.

11. Billon C, Sitaula S, Burris TP, et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chemical Biology. 2023. PMID: 36988910.

12. Gallagher C, Emmanuel OO. NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence. Ageing Research Reviews. 2026;116:103057. DOI: 10.1016/j.arr.2026.103057. PMID: 41655607.

Research Disclaimer

This article is provided for educational and research purposes only. Discussion of experimental peptides, compounds or biological pathways does not constitute medical advice or a recommendation for human use. Some compounds discussed remain investigational, may not be approved for therapeutic use in Australia, and may have limited or no controlled human clinical data for the applications described. Findings from cellular and animal studies should not be assumed to translate directly to humans. Regulatory approval of a compound for one specific medical condition does not establish safety or effectiveness for other uses.