Do Mitochondria Rule the Body?
- Thomas P Seager, PhD
- 7 days ago
- 32 min read
Updated: 4 days ago
Martin Picard PhD describes the mitochondrial perspective on human systems biology
Summary
Popular belief suggests that the genes in your nucleus hold the blueprints to your physiology. However, Columbia University Professor Martin Picard, PhD suggests that is mitochondria that really govern human systems biology. They signal cell differentiation, control expression of the genome, and initiate cell death.
New research reveals that mitochondria can transfer between cells and organs, suggesting novel therapeutic possibilities for diseases like cancer and metabolic disorders.
Mental health and motivation are closely linked to mitochondrial function, with evidence supporting the role of mitochondria in psychological well-being and disease.
The Mitochondrial Perspective
Mitochondria have long been considered the "powerhouse of the cell," but new science reveals a far more complex and vital role at the heart of human health and healing. In Episode 17 of the Uncommon Living podcast Columbia University Professor Martin Picard describes his pioneering research challenging traditional views of system biology. According to Picard, adopting a mitochondrial perspective offers a new medical paradigm that 75 years of fascination with the human genome has heretofore obscure. These tiny organelles regulate not only cellular metabolism but also control cell division, differentiation and death (Lee-Glover et al. 2025), organize hormone production, and shape metabolic flexibility across the body.
Hormonal and Therapeutic Implications
Picard explains that mitochondria are indispensable to physiological and mental well-being. He confirms that all sex hormones originate in the mitochondria, which is the answer to the question Why is Testosterone so Low? Additionally, the mitochondria govern neural development and generate the energy required for neurotransmitter balance and brain function (Andreazza et al. 2025). Disruptions in mitochondrial function can lead to mood disorders, loss of drive, fatigue, and even changes in motivation.
Understanding mitochondria offers new avenues for supporting mental health. For example, in Ice Baths for Mitochondrial Therapy explain how a regular practice of cold plunge therapy can boost mitochondrial function and reduce the rate in which they are damaged. The may explain some of the improvements in mental health among people who adopted a regular cold plunge practice, as described in Ice Bath for Mental Health.
Intercellular Mitochondrial Transfer
Picard also describes recent evidence that reveals that mitochondria are not confined to individual cells but can be secreted and transferred between cells and organs (Borcherding & Bresthoff 2023). This intercellular transfer offers a promising avenue for therapies that restore mitochondrial function, and may explain Dean Hall's miraculous recovery from chronic leukemia, described in like Dean Hall's Cancer & Mitochondria.
Emerging research highlights mitochondria’s profound influence on the epigenome, where mitochondrial metabolites regulate DNA methylation and histone modifications, thereby modulating gene expression without altering the genetic code. Such energetic regulation of the epigenome opens avenues for future therapies capable of reprogramming gene expression to alter disease progression and extend healthspan. In Chronological vs Biological Age, I wrote about how understanding the immortality of mitochondria is critical for extending human longevity.
A New Vision of Health
Picard's scientific perspective invites us to think about human physiology as a dynamic network for organizing the transformation and allocation of energy to maintain resilience under stress. His view complements Rick Cohen MD, who asks Are You Tracking the Wrong Health Markers?, where he suggests that health metrics indicating readiness for stress are better than more popular measures of peak performance, like VO2max. My interviews with both Cohen and Picard reinforce my belief that mitochondria are in constant communication via bioelectric and molecular signals, enabling adaptive, coordinated responses to environment and experience (Picard 2025). This view shifts the dominant metaphor of the body away from a mechanical, machine-like system, to an energetic information network in which mitochondrial are critical nodes of communication.
A full transcript of our conversation is below.
00:00 Introduction to Mitochondrial Science
Seager Martin Picard. Thank you for joining me on the Uncommon Living podcast. I found you on Twitter teaching the world about mitochondria and I knew I wanted to talk to you.
Picard Thank you. So happy to be here.
Seager What I'm trying to do with Uncommon Living might remind you of graduate school, where you have seminars and speakers come visit on campus and they talk about their area of expertise and there's no grades, but you get to ask questions, you get to learn really interesting things that broaden your understanding and help you see connections between your field of expertise and adjacent fields.
This is what Uncommon Living is for me. It's like my own graduate seminar series. There are very few of our listeners who are really signing up for that experience. And we might dive deeper into the science of mitochondria than social media would ever tolerate. But here's what we're not gonna do. We are not gonna talk about how mitochondria is the powerhouse of the cell.
Picard Love it.
Seager Everybody that listens to me understands that. What they don't get is that many of the analogies, the mitochondria are like a battery, the mitochondria are like a power plant, many of these analogies are oversimplified to the point of being wrong. And this is why I wanted to talk to you, because you don't waste your time talking about ATP. although you do say, look, it's an energy converter, you know, and that's very useful.
You talk a lot about the more advanced things that mitochondria do in our body. That is, they are more than just ATP producing agents. And you probably have a sense of what you'd like the audience to know besides converting metabolites into ATP. Will you give us an intro?
Picard Sure. Thank you. This is awesome. Yes. Your graduate seminar style, I think is the way to go. We need deeper type conversations. And so thank you for having me. I really appreciate the opportunity. My country are living creatures. There's small living organisms that populate our whole body. Every cell except the red blood cells have hundreds or thousands of mitochondria.
And they came from this evolutionary merger of one little cell that was able to use oxygen or transforming energy, the other that couldn't, and then they came together and then that's called endosymbiosis. And if you take the perspective of, you know, the big anaerobic cell that, you know, is basically the ancestor for what our cells are, then you think that they kind of tamed the mitochondria and then the mitochondria are in service of the cell and the nucleus maybe and you know the almighty genes and the blueprint. Another perspective that I think is equally likely is that the small aerobic breathing bug that became mitochondria actually took control of the big cell and then we really are a mitochondrial collective and our lives are driven by you know the desire, the drive of mitochondria to get oxygen, to get food and, you know, to be fueled up and to flow energy. So I think that's that mitocentric perspective is equally relevant. And then mitochondria we realize in the last 20 years in mitochondrial science, they do so much more than making a TP. They make hormones, they regulate calcium in the cell. They have a veto on whether their cell lives or dies.
And so they have this control of the mitochondrial collective inside the cell, not the nucleus, the mitochondrial collective senses that this cell is no longer needed. Their existence is no longer needed. There's kind of a social contract that binds every cell of your mitochondria in the body. And that those mitochondria will say, okay, time to die. And then they send the signal and the cell dies. Whether if you're a stem cell and you're
Picard You need to decide is a time to commit to differentiate into a neuron or into a liver cell or into a muscle cell or that commitment, that differentiation, which is a life transition in very real terms, that is driven and controlled by mitochondria as well. So there are all of these cellular decisions and behaviors that are actually driven by metabolism and energy flow and mitochondria. that's how, you know, we could talk for much longer about this, but in a nutshell.
We understand mitochondria as an information processor, something that integrates information and then kind of translates this and integrates that in a way that can better guide life and cell-cell interactions.
Seager This is a huge leap ahead in our understanding of human biology, of human metabolism. Because when you take that mitochondrial perspective, you realize mitochondria have their own DNA. You realize mitochondria have their own life cycle. They have their own reproductive cycle. And it's nothing like what we learned in high school biology. The mitochondria are inherited exclusively along the maternal line and they reproduce. Asexuality there are mechanisms inside the body that will allow the mitochondria for example to proliferate So we might brown our white adipose tissue by multiplying mitochondria and turn it into a thermogenic organ rather than just energy storage.
You're suggesting it's very provocative to suggest that mitochondria have a life of their own Inside the body and that might lead us to ask questions about mitochondria that we otherwise might overlook. Is that what you're going for?
06:55 Mitochondria in Human Health
Picard Yeah, exactly. think the mitochondria do have a life of their own, but their life is very much intertwined with our lives. And what's clear is that when your mitochondria thrive, then so, so do you, right? And our ability to be at our best requires that our mitochondria are working well. And there's lots of good evidence that if your mitochondria not working properly, transforming energy or making hormones or doing other things, you cannot be you as a person. You cannot be at your best physically, mentally, and I see examples of this every week. I, I'm not a clinician, but I'm in the clinic half a day a week and I see patients with rare, genetic defects in the mitochondria. if the DNA that encodes parts of the, of the mitochondrial, energy transformation machinery, which, as you said, we get from the mother, when there's a defect in that mitochondrial DNA, this leads to, an inability to transform energy efficiently. So I see human consequences of that regularly and it's mitochondria are important for so many different organs, functions and our own state of mind and state of consciousness.
Seager Even changes to personality can originate in mitochondrial health. Chris Palmer has this book, Brain Energy, where he's able to treat, or he talks about treating psychological disorders, mental health disorders with a keto diet or other therapies that target mitochondria. And then Ben Bickman comes along with Why We Get Sick. And he says, look, all the leading causes of death from chronic illness in the United States originate in insulin resistance. And we know insulin resistance is associated with mitochondrial dysfunction. But what I picked up along the way is that mitochondria are the site at which all sex hormones originate. So whether it's testosterone or even cortisol or pregnenolone, which is a sex steroid synthesized on the inner mitochondrial membrane.
If your mitochondria are not in good shape, it's no wonder you don't feel like yourself. You might lose your motivation. You might lose that zest for life that gets you up off the couch. And then when the mitochondria are restored, you can literally feel like you're a different person.
Picard I think that's quite possible. At this point, I would say it's a partially supported theory, right? The mitochondrial theory of mental health or mental health disorders as metabolic disorders. I think there's a lot of strong evidence that says this is correct. If you don't feel well, right, then you don't feel like yourself and you feel terribly depressed that you want to die. Or you have bipolar disease that you fluctuate between states of mania and states of deep depression.
Or you see, hear things that other people don't hear and you're kind of, have some dissociative experiences and schizophrenia. All of this is not because your brain is broken. Your body is not broken. You're not a molecular machine. You are an energetic process fueled by your mitochondria. And if energy isn't flowing properly, you as a person, your energetic self changes. And when that happens, you this might be the most, you know, first principle understanding what diseases, right? This ease when you're not at ease, this can happen probably very quickly because your energy isn't flowing properly. And we, we, there's some example, historical example. I, I learned this when I was in graduate school, I was learning to, study mitochondria, mitochondrial respiration, right? One major way in which mitochondria do all of these things, including making hormones, those you know, the sex hormones that give the women body, the female body, the ability to conceive new, to carry new life, right? Progesterone, estrogen, those are made in the mitochondria. This is amazing. And testosterone determines whether you get a penis or not during embryogenesis. Testosterone is made in your mitochondria. So these are, these hormones are the basis for you, for the survival of our species. And for some reason that nobody understands, their, their synthesis was, you know, converge in the same organelle, the same cellular site that responsible for keeping the lights on and making decisions about, you know, cell life and cell death. So I think there's a profound connection there between energetics and, you know, survival of the species and mitochondria are kind of the hub for this.
Seager And we got to understand how these mysterious organelles work a lot better. And I'll give you one example. You have told the world that mitochondria within the cell, they will fuse, they will fission, they are dynamic. They're capable of cooperating under the conditions of stress or whatever is called upon them. But here's something I want to know. Do mitochondria transit from one cell to another. Can they travel through the body?
Picard Yes, there's now very good evidence of inter organ mitochondrial transfer.
Seager Martin, this is remarkable. I mean, this is profound. What it means is you may have something going on in your liver. Let's just, I'm picking examples, right? You might undergo a therapy. And of course I'm thinking about ice baths. Ice baths stimulate mitobiogenesis. But we think of that as happening in the fat cells. We're going to make more brown adipose tissue or whatever it is.
Seager What you're saying is that mitochondria synthesized in one cell could travel through the body into a new cell and perhaps rehabilitate a cell elsewhere using mitochondria that were produced somewhere else in the body, that is remarkable.
Picard This is not what the textbook teaches you. This is, this is, that is not what I learned in my undergrad or grad seminar. So kudos for this seminar where you're, you're learning the cutting edge of mitochondrial biology. We don't know if this happens in humans. I mean, it's clear that it happens in animals, you know, in mice. If you inject mitochondria in the bloodstream of a mouse, first, the surprising thing is that nothing bad happens.
Seager Correct. Hahaha.
Picard It, you know, as if this was natural. And then if you take the blood of human beings and you look at it and you look at it under the microscope and we have a paper that's should be coming out to the next few months showing this, you see mitochondria, they're a whole floating in the blood. Yeah. So a few questions then, you know, emerge is like, first, what are they doing there? It's a good question. If you want to know what something's doing in biology, it's often very useful to know where did it come from, right?
Seager Incredible. What are they doing there? Yeah.
Picard Like where did they come from? What made or secreted those mitochondria? And then number two, where are they going? And so there's a few scientists, my good friend, John Brestoff and Wash U St. Louis has been studying this for many years and found in mice, for example, that the adipocytes of fat cells can secrete mitochondria in the blood and then those mitochondria can go to the heart and then the heart will take them up. So there's evidence of inter organ mitochondria transfer like this. And now we know there's a bunch of cell free mitochondria that are outside the cell, right? That's cell free means. That's not again, what the textbook says. And where did they come from? I don't know. The best hypothesis I think is they come from the bone marrow. There's, know, inside your bones is where all of your immune cells are made. That's where, you know, some people think that the cell free mitochondria come from. That's a dedicated organ.
The bone inside your bones. It's a dedicated organ to what's called hematopoiesis, making new blood cells. So maybe those same cells, those same processes are also dedicated to, you know, not just making immune cells for the whole body, but making mitochondria for the whole body.
Seager If I had to bet, I would wager there is not one single source of those cell-free mitochondria in the bloodstream. The body is so complex, and the cells within it were constantly discovering new functions of cells that we thought had this purpose and this purpose, but actually have these secondary functions that turn out to be very important in the body. Just the one that you mentioned, that fat cells can release mitochondria has profound implications for mitochondrial therapies because I know how to access those fat cells. I know how to stimulate mitobiogenesis within those fat cells. What I don't know is will the mitochondria from those fat cells reach tumors? Because there's a lot on tumor metabolism and we understand that cancer originates in mitochondrial dysfunction.
What we do not understand yet, despite Thomas Seyfried's appearance on, know, Steven Parlett's Diarrhea of a CEO, what we do not understand is once the tumor is present inside the body, how do we really correct the mitochondrial dysfunction? And there's lots of ideas about starving it out. When it's glucose dependent, we will go keto. But what we don't really know is whether the mitochondrial function in those tumor cells can be restored.
Certainly, apoptosis might be signaled by a restored mitochondria, but perhaps the cell could be corrected in its function. There might be a myriad of ways that we would target cancer cells through the mitochondria once we know that the mitochondria are more fluid than we thought. Reaction?
Picard Yeah, one perspective on cancer that I think is likely to be correct is that what allowed the difference between a cancer cell and a cell that's part of this body, a healthy cell, is that the healthy cells are all bound by some kind of social contract, right? Every cell works in unisonhyp and coherence ideally with every other cell in the body. And when you have one cell that says, nevermind, like I'm out.
And then it basically starts to focus on its own small little self. Mike Levin, who studies bioelectricity and thinks about cell collectives, speaks in terms of the collective self, like every cell together, bound together by bioelectricity and other things, behaves as a unified whole. And then you have the small self, like the one cell that just works for itself. So cancer is in a way a cell or a few cells from the collective that basically goes out on their own reverting back to their ancestor, know, pre endosymbiosis before they acquired mitochondria. Cells were bacteria. The only thing they cared about presumably was to make more of themselves, right? And that's basically what a tumor is. So you can think of a cancer cell as a cell that's reverted back to its ancestral nature, right? It's forgotten that it's part of a greater cell collective.
18:50 Mitochondrial Transfer and Cancer
Picard My hypothesis is that what endosymbiosis did when mitochondria came in, it basically gave cells a higher order cognitive ability, if you want to use a metaphor, that made cells social, right? It gave the ability of cells to talk to each other and to entertain a greater collective, a greater collective purpose, if you want. And what you see in cancer, where the cancer cells are not respiring, they're not using their mitochondria. My interpretation of this is that cancer cells basically have lost touch with their mitochondria. The mitochondria are still there, but instead of giving the signals and giving the cues to the cell as to how to behave so it can be part of the social collective that we call the organism, the cancer cell ditches their mitochondria and instead they start to use them for biosynthesis, to make building blocks so they can grow as fast as they can. So I don't think of the Warburg effect, right, which is cells that will do glycolysis even though there's oxygen. They're, you know, they're not using the mitochondria even though they could. My interpretation of this is not because the mitochondria are dysfunctional. think mitochondrial dysfunction is a term that assumes implicitly it means there's only one function and that one function is dysfunctional, right? It's not happening the way it should. So this brings us back to mitochondria powerhouse.
Seager Great point.
Picard I try to never use a term mitochondrial dysfunction because it, it singles out mitochondria as a power plant or powerhouse. so there's something different. There's a recalibration that happens biologically and then the cancer cells ditches their mitochondria, and re-engaging the mitochondria, right? And kind of bringing the cell back into this oxidative metabolism might be the way. And that might be how, you know, cancer cells eventually die or, know, end up reintegrating the cell collective and there's even experimental data. That's the case if you force cells to to be oxidative by you know keto diet or glucose deprivation you might force a cell to say okay the cells that I can't use this ancestral glycolytic anaerobic metabolism I need to use my mitochondria but as soon as they start using the mitochondria energy flows in a way that pulls them back into the cell collective. So I think this is likely to be true. We don't have direct evidence that this is the right interpretation, but the alternative interpretation that, you know, cancer is driven by mutations and that there's like, don't think the evidence doesn't stack up. was a popular and yeah.
Seager It's no longer worth investing in. It's just not credible. have some 50 years on the somatic mutation theory. Where has it got us? Your ideas are much more thought provoking because this mitochondrial perspective requires that the mitochondria are communicating with one another, that they are coordinated throughout the system of the body. Typically, we would look for chemical signals inside the body as the mechanism of communication. And I think that might be slow, inefficient, probably not the way mitochondria are communicating. Perhaps mitochondria communicate with energy instead of with chemical material. Perhaps it is the biophotons that they are producing which are reaching neighboring mitochondria that create a network of light throughout the body that coordinate the actions of them. What do you think?
Picard I think that's possible. think it's possible. Ultimately, think our essence is energy. Like we are energetic processes. so yourself fundamentally is the movement of energy that happens, right? And I think we know this and it's pretty clear when you think about
What happens when you die, right? Is that the flow of energy stops. The body is still there. The cells are still there. The genomes are still there. The connections in your brain, the synapses, everything is still there. And your organ are still all in the same places. The body, the physical stuff is there, but you're dead. You're no longer, right? What you are is the movement of energy. And I suspect...
Seager We are an organized flow. There's this word in engineering, exergy, that I teach to my students. We are an organized flow of entropy producing. We take exergy, we convert it to entropy, but not just dissipation of low temperature heat. That process of entropic production is organized by the structure of our body. And it is that flow of exergy that creates the structure, or I should say maintains the structure.
Picard Yes.
Seager And I agree with you entirely. We are thermodynamic creatures, but not in the sense of an internal combustion engine, because we are self organizing. And many of the analogies of the industrial revolution, your brain is just a fancy computer, are sort of insults to the beauty of the complexity of the human body. Regardless, it is that flow of the capacity to do work that we rely upon as living creatures, and all biological and ecological systems rely upon it..
Picard Correct. And to answer your question about molecules and metabolites and yes, cells communicate. know this, cytokines and there are other chemicals that are used, hormones, neurotransmitters for cell-cell communication. If we think from first principles and we ask what is a hormone and where does it come from? Where did it come from in evolution?
24:46 Energy, Information, and Consciousness
Picard Hormones and cell-cell communication messengers, these are I think fundamentally crystallized patterns of energy. And you can imagine, you know, back in evolutionary days, if there was like something really stressful that needed a lot of energy, this is like a whole body distributed, you know, an energy pattern, right? Like to survive, you need to mobilize a lot of energy. And if you need to kind of reprocess that signal, that state to survive, then it's probably very slow. And then every cell in the body needs to know that there is emergency. So probably at some point, this distributed kind of delocalized energetic state crystallized into a hormone we call cortisol. Right? So now the result hundreds of millions of years later is that you have your cells, every cell in your body has this receptor is called the glucocorticoid receptor. And then every cell knows instantaneously if cortisol comes and binds that receptor, means like shit is about to happen. There's something dangerous out there.
Get ready, you know, make more mitochondria and maybe, you know, get ready for a potential insult. and, that, you know, all of this costs energy, but the point is that, there's every hormone, every metabolite, every, you know, protein probably is in some way condensed energy, right? That has a specific pattern of energy that gets condensed. And then it has very strong, you know, powerful meaning dopamine, serotonin, norepinephrine.
Probably all of those have this kind of crystallized energy pattern nature. So cells use those. We can't disregard this, but then there's probably a lot of other ways in which cells, other energy modalities. The chemistry, right? This is one form of energy. Chemical energy is one form. There's also electricity, bioelectricity is another form or modality of energy. Biophotons, you mentioned.
The electromagnetic wave in another form of energy. there's chemistry, electricity, light energy, there's sound, you a vibration energy, mechanical energy, kinetic energy. There are things in the body that flows that hold kinetic energy. So there's probably something there. energy is not a thing, right? And when even like the physicists don't even agree what energy is and...
Seager There are 27 different definitions of entropy in the scientific literature the last time I checked. It's very confusing.
Picard One thing that's clear is that we are energetic creatures and we harness, biology has learned to harness energy in its different forms. Chemistry is one of them. It's a slow one. And then there are all of these other ones that we've kind of disregarded when biology and medicine became, you know, all about molecules. And then there was a great hypothesis that came about in like the 60s, 50s that we are molecular machines.
And by sequencing the genome, we're going to understand everything. And I think that was a good hypothesis. It's us. Yeah, but I think that hypothesis has been effectively disproven and it's it's a useful model for some things. Like if you're in a car accident and you have an artery that's broken open, it's useful to consider the body machine. If you're giving birth and the baby is not coming out because of some issue.
Seager It was fun while it lasted. Yeah. I agree.
Picard And then you need to do C-section. It's useful to think of the body as a machine. But when it comes to understanding health, which is a state and healing, the healing process, which is a dynamic unfolding living process, these things are not mechanical and, uh, and life and the healing process is something that happens in nature. And you see this beautiful movement of, you know, things, trees, plants, you know, and healing and growing, uh,
Machines don't do this. And so I think it's very clear. We're not molecular machines, even though we use, you know, material parts and there's a physicality and a molecular dimension to our existence. But our fundamental nature is not that, you know, mechanical dimension.
Seager I'm so glad you're bringing this up. One of the things that I was just done in this undergraduate unit that I have in engineering, all civil engineering students, we go over why thermodynamics is so confusing. It has essentially gone through three different eras. And students don't understand this. The second law was discovered before the first, and then we had to invent the zero-eth law, because we didn't really understand the way the first worked. Entropy was formulated in an era in which engineers were concerned with mass, sorry, with heat transfer. Heat transfer was the first problem that motivated this abstract concept of entropy. And it was Boltzmann and some others, James Maxwell, who realized that entropy could also be applied to mass transfer. And they were really the same things. It was the 50s and 60s when that era changed, we realized that information transfer was another way of understanding entropy. And this was due to Claude Shannon for the most part. Now, it is more than just an analogy. The equations of heat transfer that also apply to mass transfer, that also apply to information transfer, are a universal way of modeling every action that happens within a living system. When you say the hormone is like crystallized energy, what it is, is information encoded in the molecular structure that travels through the body and there is so much leverage that is signaling is a word we use, but telling the body because the body has no choice but to respond to the information encoded in this molecule and new things happen. This entropy of information transfer is the age that we're living in now, whether it's artificial intelligence or whatever the technological embodiment is. And it belongs in our understanding of human systems. That we are information processing systems that rely upon, yes, material transfers and energy transfers in order to facilitate this sort of higher level understanding of thermodynamics. That's the way I look at it.
Picard Yes, agreed. Information is, you know, pattern energy. You take raw energy and then if you pattern it, you give it a wave, right? That's what a speaker would do, for example, right? You just have flux of electrons, but then you, you know, interrupt it and then you let go. You interrupt it and then you get a movement and then you pattern air molecules into, you know, sound energy, right? So you've just taken a raw energetic signal, which in for biology would be food, right? Food has the energy potential of the chemistry, the electrons that are stuck on carbon, you know, that is condensed sunlight. And then there's energy potential there. Then when you put this into your body, your body patterns that energy into information, right? Into cell leader structure, into mitochondria, into hormones, into metabolites and so in a way, of the hormones and the chemicals that are in the body, they're like footprints of underlying energetic processes.
Seager Well, it might sound like a subject change, but I think it's related because there's somebody I've been wanting to ask you. Richard Fry told me that the mitochondria control the landscape of the epigenome. Now, we know that there's information encoded in the DNA, but is the epigenome that says which of those genes will be expressed and which will not? The idea that the mitochondria control which of these epigenetic markers, whether it's methylation or anything else that can turn on or off a gene is an incredibly powerful thought. Now the mitochondria, which are sensing the environment and adapting inside the body to the conditions that they're sensing, it is the mitochondria that are governing the landscape of the genome. Martin, I've wanted to ask you, how could that possibly work?
Picard If you look at the textbook and it's a modern textbook, so it talks about epigenetics and it will say, you know, the genome is the blueprint for life. It has the information for all of life. But then you look at the genome and nowhere in the genome does it say that the organism is going to have five fingers or it's going to have four limbs. Right. So there's kind of a missing dimension, but still the textbook says the DNA has all of the information very well. But then the next chapter is epigenetics. Which epi, you know, the prefix means on top of. So you have the genome, the code, and then which has about roughly 25,000 genes. And then on top of it, there are chemical signals, which might be, you know, the footprints of some energetic pattern that's, you know, hovering over around the genome. And what those chemical marks do is that they can, like you said, either turn off a gene, it's called suppression or repression of a genetic genomic element or you can activate it. So you open up the gene and then the gene can be active. so some people have, you know, the bad gene for X, a gene that predisposes, there are very few, you know, genetic variants that have a hundred percent penetrance. Like if you have this variant, you're going to get sick. Like very few genes like this, mostly they confer a little bit of, of, you know, a few percent increased risk. but if you have this like increased risk variant, but it's, it's silenced epigenetically silenced then you're not expressing it. It doesn't matter what's in the genome, the gene is not on. And that's the beautiful process that allows every cell in the body to have exactly the same genome, yet you have a neuron that looks like a neuron, functions like a neuron, and it expresses no protein that is specific to the heart, or no protein that is specific to the liver or to the fat cells.
Every cell is so unique, so beautifully different. Like under the microscope, they look different. They function differently. They burn different food. They produce different chemicals and they live different durations. And, that's all because of the epigenome. far as we understand, every cell has the same basic code, but then the way the code gets expressed, some genes get turned on and some genes get turned off. This is what determines the, the, the individuality or the specific unique characteristics of different cell types.
Seager Let's talk about the implications of that. Stem cell therapy is a big thing. I have a friend just flew down to Panama to do stem cell therapy, you know? Now these stem cells, every cell carries the same genetic information. These stem cells though can become a specialized part of the body. They have not yet sort of committed to become bone or cartilage or something else. What you're saying is the differentiation between these cell specializations doesn't happen at the genetic level. It couldn't. They all have the same genes. It happens at the epigenetic level.
Picard Yeah, exactly. And then in the last 10, 15 years, scientists started to discover that a major layer of information that, you know, that turns on or turns off what's called epigenetic writers, right? The enzymes that go and like write the epigenetic code and then epigenetic erasers that go and like erase the marks. So the writers can go into the genome and say, OK, now this gene off and then this gene on typically is done by the erasers. You remove some marks and then the gene opens up. There's a lot of complexity there, but what scientists started to realize in the last decade or so is that this writing and erasing is actually done by metabolites. Like the signals, the cues, right?
36:55 Mitochondria Control the Epigenome
Picard That turn on or turn off the writers and the erasers are actually metabolic cues. And then if you look at the specific chemistry of the epigenome, you realize like the majority of these epigenetic marks, DNA methylation or acetylation of the histones or other kinds of modifications, they all require metabolites or cofactors that mitochondria make. then mitochondria, if you kind of look at this side, where do these signals actually come from? The majority of those signals either come from directly the mitochondria or their, you know, mitochondria indirectly contribute to them or, you know, the bioavailability of the epigenetic marks. Uh, and then from an evolutionary perspective, this probably makes sense. Like imagine you're a cell, you just underwent endosymbiosis. You have these new like breathing bacteria in yourself, and then you want to know like, do I have enough energy to, divide, right? Or if I begin division and I burn all this energy dividing, am I going to die in the process because there's not enough energy around. So then how do you know if there's enough energy around?
To do this very energetically demanding thing that is dividing.
Seager You must rely upon metabolic signals.
Picard Exactly. And then those metabolic signals very quickly, they started to come from mitochondria because mitochondria were in charge of aerobically using oxygen to transform energy. it makes, you know.
Seager Martin, the normal approach to gene therapy is to try and edit the human genome. But what you're saying is mitochondrial therapy is gene therapy. Instead of changing, you know, DNA strands around, we can turn them on and off if we understand how to stimulate the mitochondria to do it.
Picard Yeah. I wouldn't call this gene therapy. would call this, you know, metabolic therapy or, know, some energy based or energy informed therapies. And once you start, once you realize that you're an energetic creature, that, you know, the, the, the physical molecular aspects of your body is not what you actually are. You are the energy that flows through this. It makes you think really carefully about the things that you put in your body and then how you, what you might do to enhance your health or to, to heal from a disease. And mostly from this, you know, mechanical view we've had of the body as a molecular machine and ourselves as a molecular machines, all of the interventions and most of the therapies we have are, you know, drug-based. So they target this molecular machine layer. Uh, there are other therapies we've known for, you know, centuries or millennia that are, you know, useful, like exercise is good for you. Why is that?
Well, maybe exercise is good for you, not because it does something to your molecular machine. We know it does, but maybe the actual locus of action for exercise is because it makes your energetic self that which you are flows, you know, more smoothly, more efficiently. And maybe ice bath therapy is is beneficial because it kind of forces yourselves to really all come together. Right. And kind of this this hormetic way. So maybe a lot of therapies, know, breath work or meditation, mindfulness, like these things are, these practices affect your energy. You know, they, they end up kind of rippling out. Maybe the energetic effect it has on yourself ends up rippling out into the molecular dimension. And then we see changes in gene expression. We see changes in the epigenome. We see changes in the telomeres. We see changes in the mitochondria, but I wonder, you know, maybe those are just secondary to what's actually happening energetically. And the same thing for pharmacotherapy and the way we address mental health disorders and the way psychiatry has gone, I think is deeply biased by this hypothesis, right? That we are molecular machines and disorders of the mind, psychiatric disorders, or therefore because your brain is broken or it's deficient in some neurotransmitter. Those hypotheses have turned into dogmas. They're not scientifically proven, but yet we've been acting as if they are and then medicating people as if that was the cause of mental health disorders. I think Chris Palmer is probably right. Mental health disorders are metabolic disorders and the best, most sustainable approaches to mental health disorders, not to say that acutely some drugs are not useful. I think that they can be, but to treat the problem and to help people be at their optimal state of health and regain health to stimulate the healing process. Drugs are not the answer. Drugs don't heal. As unfortunate as this is, we don't have a single drug that actually triggers or stimulate the healing process. We have practices. Maybe the practices you're very familiar and your audience is familiar with, they're practices that really help the body heal itself. And healing is done by the organism, not by some external thing that we take in.
Seager Let's talk in the few minutes that we have left about consciousness. I was saying that this mitochondrial perspective requires that the mitochondria can communicate with one another. And probably that communication is not just chemical. It might be energetic. There may be another plane on which
Picard I would say that communication is definitely energetic and many different forms of energy are probably involved and chemistry, your molecules is one of those forms of energy.
Seager There might be something besides the material, besides the energy that can be picked up with our lab instruments. There might be something that transcends our instrumentation that connects mitochondria or even connects people. We have this word consciousness and there is a delusion, I think, that it resides somewhere in the complex chemistry of the brain and that's where consciousness exists. It might not.
It might be that we are antennae that tap into a consciousness that exists between people or in the interstitial spaces between the things instead. And I wonder if you have some ideas on that.
Picard I think that's likely. you, if you, if you think again from first principles about the basis of our model, uh, you know, for how we think the world works and life, uh, we, we've all grown up like fish in water. And, and, and in our case, the water is like, exactly. If you, if you've grown up in something for so long, you have no concept. It's almost impossible to imagine that there's something else in water, right? If you're a fish and that's all, know, we've grown up in materialism and physicalism, right? As philosophical assumptions that we're not even aware of. And the assumption here is that matter, little pieces, atoms, and then molecules, and is like the most fundamental thing that there is, the most, the truest layer, right? The most basic fundamental layer of existence.
Or molecules and then in the atoms and then some atomic particles and then you can go pretty deep. But then if that's the case, everything must emerge from those smaller levels, right? That's what materialism or physicalism is. And then when you get to really difficult things that feel different, including the mind, right? Like different experiences or the process of the mind and consciousness, self-awareness, then you need to, neuroscientists have been doing this for decades now, you need to make some really like spooky, you know, illogical leaps to say, yes, somehow there's like these neural networks and then out of the neural networks, somehow like consciousness emerges.
This is a real leap. And I don't think scientifically it's very hard, if not impossible to justify. And so there's some neuroscientists have come, you know, tried a great length to, come up with, with explanations or, you know, hypothesis for this and theories.
Another alternative is to say what is most fundamental is not molecules. It's this other kind of substance which we can call consciousness. Some people call it like big C consciousness. Max Planck, who is like a quantum physicist, at the end of his career, he wrote at length about this and he ended up saying, I regard consciousness as most fundamental.
Matter and everything else just emerges from consciousness, from this deeper level. David Bone, also a physicist, kind of arrived at the same conclusion. Einstein said, you know, similar things. So there's a lot of people who've thought about energy, who've thought about matter, and at the end of their lives, they're like, shit, that doesn't make sense. There's something else. There's a deeper underlying layer of reality. So my perspective on this is, I don't know what the truth is, but I suspect that there's kind of this underlying current and let's call it consciousness. Some people might want to call it God. Some people might want to call it the, you know, energy and like dark energy or whatever, you know, physical, the force. Yes. Yeah. So there's the force or the force of consciousness, let's say that is flowing. That's just energy. What energy does is it naturally seeks ways to transform itself or to, you know, to, to move into flow.
Seager The Force, you know, give it a name. Yeah.
Picard This is like a fundamental property of energy in its different forms. Energy wants to flow, wants to be transformed. Um, so maybe there's an underlying current of consciousness. We don't even have like conceptually three, four dimension that we can kind of be aware of. We don't have a way really to understand this, but let's imagine it's kind of a river as a smooth, you know, flowing river. And, um, and then once in a while in that river, you see a little Eddie form, right? A little tourbillon, a little Eddie is like, look, where did this come from? And then, yeah, a little, you know, a little structure that came out of nowhere, out of this stream. And you're like, where did this come from? I don't know. How big is it going to get? I don't know. Where is it going to go? Is it going to go left and right? I don't know. How long is it going to last? I don't know. So maybe what we are, you know, we living organisms, human beings, but every other living organisms were little eddies.
Seager A structure.
Picard Right. That spontaneously form more or less spontaneously through the, you know, the product of other living creatures interacting with one another, reproducing. So we're all little eddies, you know, that have unpredictable courses. We don't know how long we're going to live. We have averages and we tried to predict and understand this, but we don't know. And then every, every little Eddie is unique. Right. And it emerges spontaneously out of this greater current. So I think that's,
It's a worthwhile hypothesis. then it brings to, it brings us to think, you know, from first principles about the nature of each of our movement, but also to see ourselves as movements and then, an energetic movement. we're always in flux, always changing. there's some kind of, structured or some, you know, an eddylooks like another eddy, but there's a lot of differences. It's the way that human beings look.
49:03 The Case Against Reality?
You know, lot of features we share, but we're also very different. And we have genetically identical human beings, know, monozygotic twins that are so different and personalities and their likes and dislikes. Where does this come from? I don't know, but maybe there's a deeper layer of, of, of organization that, you know, precedes the molecular structure of our genomes and other things. So we can't...disprove this. And the same way that we cannot prove and that the materialist or the physicalist viewpoint is superior. So at this point, there's been very good arguments made by Don Hoffman, who wrote this beautiful book, The Case Against Reality, who makes the same point that matter is not most fundamental. Despite what your senses are tricking you into believing, matter is not most fundamental. There's another layer. And then you're an expression of that layer and your own conscious experience is in a way this movement of consciousness or energy that is experiencing itself. And so this leads to really interesting questions and hypotheses which I develop in the book that I'm writing called Energy.
Seager Wonderful. This has been a terrifically intense little grad seminar podcast. Thank you for joining me. I know I should let you go. And there are still so many questions to ask. Perhaps we'll circle back on some of the more mundane ones in several months if our audience has even made it this far through this one.
Picard Sounds good. I'd be happy to. Thank you so much. Very stimulating. Yeah. Thanks.
Seager Thank you, Talk to you soon.
References
Andreazza AC, Barros LF, Behnke A, Ben-Shachar D, Berretta S, Chouinard VA, Do K, Edwin Thanarajah S, Ehrenreich H, Falkai P, Ford J. Brain and body energy metabolism and potential for treatment of psychiatric disorders. Nature Mental Health. 2025 Jun 25:1-9.
Bikman B. Why We Get Sick: The Hidden Epidemic at the Root of Most Chronic Disease--and how to Fight it. BenBella Books; 2020 Jul 21.
Borcherding N, Brestoff JR. The power and potential of mitochondria transfer. Nature. 2023 Nov 9;623(7986):283-91.
Hoffman D. The case against reality: Why evolution hid the truth from our eyes. WW Norton & Company; 2019 Aug 13.
Lee-Glover LP, Picard M, Shutt TE. Mitochondria–the CEO of the cell. Journal of Cell Science. 2025 May 1;138(9):jcs263403.
Palmer CM. Brain energy: A revolutionary breakthrough in understanding mental health--and improving treatment for anxiety, depression, OCD, PTSD, and more. BenBella Books; 2022 Nov 15.
Picard M. The Social Lives of Mitochondria: When these energy-giving organelles thrive, so do we. Scientific American. 2025 Jun 1;332(6):50.
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