Ari Whitten explains how mitochondria switch between energy and defense modes depending on stress. Exercise, fasting, heat exposure, and certain plant compounds trigger hormetic stress that strengthens these cellular powerhouses and builds resilience.
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It really feels like if we're talking about environmental toxicants, autoimmunity, chronic disease, we really need to talk about mitochondria.
That's right. And actually cellular resilience revolves around mitochondria.
So what upsets the mitochondria?
Yeah, so. So there's two layers to this story. Mitochondria are either going to operate in energy mode or defense mode. To the extent that they are perceiving, they're either in a safe environment or to the. To the degree that they are sensing that they are in a, in a dangerous environment, in a stressed environment or overly stressed environment, when that stress level exceeds their capacity to handle the stress load and maintain health and homeostasis, they. They say, okay, we're under a severe enough attack that we're going to turn down energy and shift the body's resources towards cellular defense. Dr. Navio calls Mitochondria the central hub of the wheel of metabolism.
What's crazy about this is mitochondria are not part of us, even though they are part of us. They're symbiotic, so they work in conjunction with our system, but they're so now ingrained and integral in the process that we can't do it without them. And they run the show, but they're not actually part of us.
Becomes like a semantics issue at that point. But certainly they, you know, the theory is, of course, that they did not originate as part of us. They have their own DNA that is separate from our DNA. They have mitochondrial DNA. And there's a number of characteristics of mitochondria that resemble, resemble sort of primitive proteobacteria. So the idea, of course, evolutionary is that, you know, ancient eukaryotes sort of ate. Yeah, like phagocytized, you know, these, these ancient proteobacteria, and then incorporated them. And they formed a symbio, a symbiotic relationship. Sort of like, yeah, maybe this won't resonate with a lot of people. I was very into marine biology and coral reefs when I was young and studying coral reefs. Most of these corals, all these beautiful colors, these pinks, these purples, blues, all these beautiful colors are actually from. Not from the coral itself, but from an algae that lives inside of the coral animal that is called zooxanthellae. And that algae is actually another organism, but it lives inside of the tissues of the coral. And they are. They have a mutually beneficial relationship. The xanthelae performs photosynthesis from the energy of light and then provides energy and nutrition to the coral. And so it's two organisms that literally exist inside one another. You know, we also. This is not so hard to swallow. We have this microbiome. We actually have more bacteria living on. And in us, we have more in terms of numbers than we do actually of our own human cells. So we're very much an ecosystem. And mitochondria can be seen as part of that, too. But, you know, the old central dogma of biology was that DNA is the big boss, right? The nucleus of the cell has the DNA and it issues the orders about what the body's doing. And we now know through the science of epigenetics that environmental signals get translated by elements of the cell and then communicated back to the nucleus that influence gene expression. What, what genes are being expressed and therefore what proteins are being created. And actually the mitochondria, as these sensitive little danger sensors, environmental sensors, are constantly in charge of signaling. This is a process called retrograde signaling, signaling back to the nucleus of the cell and influencing what genes are being expressed. So the mitochondria are actually, which, as you pointed out, are almost. These other organisms living inside of us are actually now communicating to our DNA about what genes should be expressed or turned off.
So let's transition then to the things like stress that would cause the mitochondria to react in a way that we don't want them to react to essentially put you into danger mode instead of thriving mode. How bad does it need to be? Or is it all stress?
Let me add another wrinkle to the story, okay, that will make this even more fun and complex. It turns out that your mitochondria, Mitochondria also require stress to express optimal function. So our mitochondria are dynamic and they are directly involved in handling the body, the stress load on the body, okay? And if you, if you've ever broken a bone, if you've ever broken an arm or a leg, and you've got a cast on, and you put that cast on for eight weeks, and eight weeks later, you go to the doctor, you get your cast on off you, you look down at your leg, and it's half the size of the other One, it's half the size as it was eight weeks prior. Why? Because all that muscle atrophied as a result of not being stimulated and challenged. What challenges it use? Using it, challenging the muscle tissue, engaging those muscle tissue to handle a certain demand or stress load or mechanical load, whatever you want to frame it. Um, but if you do not challenge that muscle tissue, if you don't stimulate it and use it and challenge it to do work, it atrophies, it shrinks, it shrivels, it dies off, okay? The same exact process happens at the level of the mitochondria. And it turns out that humans are required to have a certain level of stress. And particularly certain kinds of stressors are uniquely good at this, which we can call hormetic stressors. And those stressors challenge our mitochondria. And by challenging them and actually temporarily stressing them, temporarily causing an increase, a spike in reactive oxygen species or free radicals or oxidants, and even potentially creating a small amount of damage to them, they actually engage a response that makes them grow bigger and stronger and more robust and also increases their own. What's called the. Are the antioxidant response element. And that's their own internal supply of critically important antioxidants and detoxification compounds, enzymes, okay, things like glutathione and catalase and superoxide dismutase. And it turns out that in order to keep the mitochondria big and strong and to maintain lots of them, and to maintain that are the antioxidant response element. This internal antioxidant and defense detoxification system. To maintain it in a robust way requires regular exposure to stressors. To these hormetic stressors, mainly things like physical exertion, exercise, thermal stress, heat and cold, things like fasting or occasional food shortage, things like hypoxia, either from altitude or breath holding or combined with exercise and certain kinds of chemicals, especially what are called xenohormetic phytochemicals. These are certain compounds from plant foods, things like curcumin and resveratrol and pterostilbene and different flavonoids and polyphenols and um, and. And a few other compounds. And all of these compounds act in this hormetic fashion. They temporarily stress the mitochondria by causing an increase in free radicals. And in so doing, at low doses, those stressors actually stimulate not only the. The. The mitochondria to adapt to handle that stress load, but they actually have a, a response that goes beyond that. They actually increase their capacity, even beyond what's needed to handle that stress load, creating a buffer. And so this process is fundamentally where cellular resilience comes from. And we often think of resilience as this purely psychological phenomenon of, you know, what traits make somebody resilient or not? And, like, this person went through this hard experience, and they were very resilient. But there is actually a physiological resilience that to a large extent dictates how well our body can cope with everything from psychological stress to poor nutrition to sleep deprivation to environmental toxicants. And this, what I just explained, is the basis of that process.
