• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

Heteroplasmy, mtDNA, Protein Uncoupling Response, and Glutathione.


Senior Member
Here's a link to another similar thread on this group. http://forums.phoenixrising.me/inde...eteroplasmy-of-human-mitochondrial-dna.43445/

As you will recall there is also an 81 page discussion on data science related to the Protein Uncoupling Response mechanism http://forums.phoenixrising.me/inde...ponse-and-a-possible-treatment-for-cfs.37244/

What I have discovered, much as I suspected, and thanks to listening to Douglass Wallace's video and Jack Kruse, is that UPR is central to environmental mitochondrial based disease, and mitochondrial genetic deviations are the central player in chronic environmental illnesses, or neolithic disease. This is not to say that hereditary nuclear genetics and non environmental causes are not involved in chronic fatigue, but that it is not the only player majority of the time. Rather the diseases are driven by both, but by a quantitative, cumulative loss of integrity to mtDNA. And more so, my experience with this group has been that most people here have some sort of background of exposure or toxicity, mold, metals, pharmaceuticals, etc.

I'll put this up just to get the point of what this post is going to be about, right for start.

From Mario at the 81 page thread

Quite possibly, a key Element behind our problems has to do with Endoplasmic Reticulum (ER) stress, Misfolded Proteins and the the subsequent Unfolded Protein Response (UPR). Anything that impairs proper folding of Proteins within the ER ultimately leads to UPR and the Majority of our problems. At the end of the post you can find relevant References regarding why Methylation problems, Tetrahydrobiopterin Production Impairement, Celiac Disease, N-Linked Glycosylation impairment (among others), all create Stress within the ER and then signal a UPR.


Here's my take away. Parasympathetic dysfunction, low glutathione, liver damage, and a failure to uncouple proteins and usually histamine type symptoms show up in a lot of these people. Including me. And I didn't take those drugs. But I have multiple metal toxicities. I have racked my brain over this stuff for almost a year and a half trying to figure out why I had certain kinds of symptoms. When I found this guy's thread looking for explanations about histamine I was blown away.

And then I listen to this episode of Kruse's podcast. http://podbay.fm/show/578597740/e/1383807600

Now this is KEY. Listen, very closely to the 33:30 minute to 38 minute mark, where Kruse is talking about cysteine, redox potential, current of flow on your innermitochondrial membrane, glutathione, and protein uncoupling.

Having metal toxicity personally, and struggling with the research on it for five years, I've been doing research on how to fix glutathione more than just about anything else. Glutathione and redox are at the heart of this issue, which is why the drug lipoic acid is the immanent thing to be used. I've been studying what lipoic does for over five years. It's a bit of a super drug.

Here's a mind blowing discussion by Douglas Wallace on what hetereoplasmy is, and what the effect of mtDNA variant mutations are. Basically, it is driving phenotypes of neolithic disease. This means all this 23 and me data has to start looking at mtDNA specifically, at heteoplasmy specifically.

The more heteroplasmy you develop due to mutations, stress, and pollution, the more cysteine and mitochondrial function are compromised, the more protein coupling is compromised, the more rapid these diseases develop, the worse off glutathione is going to be. You can see from his video that lipoic acid and the pathology of many environmental insults have a direct relationship if you see it from the perspective of mitochondrial physiology and mitochondrial genetics.



Senior Member
What I'm basically saying is that circadian biology drives mitochondrial health, and mitochondrial health drives neolithic disease.

CFS needs to look at circadian biology and mitochondria.