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No Longer Naive in the Ways of The Beast
After having lived for years with ME/CFS, Jody Smith learned there's more to this beast of an illness than she realized, and that what might help one person may not help others ...
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In Brief: Mitochondria and ME

Discussion in 'Phoenix Rising Articles' started by Firestormm, Oct 17, 2013.

  1. Phoenix Rising Team

    Phoenix Rising Team

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  2. peggy-sue

    peggy-sue

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    I fell very strongly, from my own symptoms, that mitochondrial dysfunction is at the root of what is wrong, not something downstream from it.
    My ME is downstream from my mitochondria not working. :p
    Every cell, every organ and every system in the body depends on mitochondria working properly.
    My every cell, my every organ and (nearly) my every system do not work.o_O
  3. peggy-sue

    peggy-sue

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    Just one wee minor thing of interest missing from this excellent article - which is that the mitochondria are inherited down the female line.
  4. Legendrew

    Legendrew Content team

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    Indeed they are - as an organelle within every cell they are located in the ovum of a mother - the sperm simply serves to combine with the DNA of the ovum and none of its mitochondria are incorporated. Interesting point and one that admittedly I forgot to include although the article was getting pretty long already! Perhaps not entirely relevant but then again we have yet to either confirm or deny whether ME can be passed down through genetic defects etc. The picture is further complicated as despite the mitochondrion having its own DNA, some of the mitochondrial proteins are produced by the normal cell DNA - presumably some of the mitochondrial DNA was incorporated into the cellular DNA millions of years ago.

    It all comes down to that pesky non-homogeneous grouping of ME. For some mitochondria likely play a much more central role however it appears that for the majority mitochondrial issues aren't as paramount as other areas, the trouble is that mitochondria are indeed central to nearly all cellular activity so even a small degree of dysfunction can cause a wide range of seemingly unconnected symptoms. The reason for my personal view of mitochondria not being central to the pathology is simply the lack of evidence and research to support it, although even if it is a downstream problem that isn't to say it could contribute to or even cause many of the ME symptoms. Another interesting point I didn't include was that there are other energy carrying molecules in the body with very specific function such as GTP which is used primarily in the transfer of proteins and chemicals in and out of the nucleus membrane. It just goes to show that the more we look into these things, the more complex it gets!

    Glad you liked the article anyway!
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  5. peggy-sue

    peggy-sue

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    The proton pump is is a bit of bio-engineering that never fails to impress me.
    Every single one of our cells can strip an electron off a molecule.... and keep it off.

    Has physics managed to do that yet?:p
  6. Legendrew

    Legendrew Content team

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    It is pretty amazing, a perfect example of the complexity evolution can achieve through small advantageous steps. I always think that it's amazing that a proton motive force and electrochemical gradient have evolved in perfect harmony with the ATP synthase enzyme to convert chemical and electrical energy into kinetic energy and then back into chemical energy, and how this all occurs simply to phosphorylate ADP. It's easy to see why a single problem could cause the whole system to back up and cause a plethora of seemingly unconnected symptoms.

    I couldn't speak for physics unfortunately as I never studied it beyond compulsory levels, other than a little mechanics in maths - I studied biology, chemistry and maths. It always seems that we're a step behind evolution though, everything we come up with is always discovered in nature somewhere.
  7. peggy-sue

    peggy-sue

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    I don't like physics myself.
    I don't trust electrons when they're not stuck to molecules, or gently stripped off and put tidily away somewhere else.
    Mechanical stuff, levers and pulleys and vetors are fine.

    Nature is wonderful and far more amazing than any fiction.

    But I don't like that electrickery.
    Legendrew likes this.
  8. WNM

    WNM

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    Nice article, well written. However I think there is more research to suggest mitochondrial dysfunction occurs in ME/CFS.

    http://cellfatigue.blogspot.com/2013/04/mitochondrial-dysfunction-in-cfs.html?utm_source=BP_recent
    justy likes this.
  9. Legendrew

    Legendrew Content team

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    nice article there - I particularly like the following comment.

    "There is now substantial evidence to suggest systemic mitochondrial dysfunction occurs in ME/CFS and underlies symptoms of fatigue. The causes of this dysfunction could be many but likely include impaired blood flow, cofactor depletion (e.g. Co-Q10), oxidative damage and dysregulation by inflammatory signaling"

    It sums up quite eloquently that despite mitochondrial dysfunction appearing to be a downstream problem, the symptoms caused by the dysfunction can be incredibly widespread. The next article in the series relates to the cardiovascular system which links quite nicely with mitochondrial dysfunction. Glad you liked the article.
    MeSci, aimossy and justy like this.
  10. stridor

    stridor Senior Member

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    Thank-you for writing this article.
    I was wondering if about the proposed incidence of ME/CFS and CCSVI and the purported mitochondrial involvement with loss of patency of the tricuspid valve in the heart with resulting venous congestion in the brain and liver.
    Do you have any comments regarding this theory? Would limiting the brain's access to oxygenated blood be the cause of orthostatic intolerance? Could brain-fog be related to this and/or failure to clear catabolites etc?
    My brain-fog used to double if I had to stand. Again, thanks....brad
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  11. Legendrew

    Legendrew Content team

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    I have to admit i'm unfamiliar with CCSVI so i wouldn't feel comfortable answering the question without further research unfortunately. I shall look into it and perhaps post a better researched response tomorrow.

    With regard to brain-fog however I think it could well be due to dysregulation clearing catabolites within the brain. Only recently I was reading about the glymphatic system, the specialised lymphatic system in the brain which has only very recently begun to be well understood. It is comprised of many channels within the brain that clear catabolites and waste products from the neurones, especially during sleep when glial cells shrink, hence allowing for increased glymphatic flow. It has been been researched in the context of neuro-degenerative diseases and dementia however I think it could well prove to be an interesting line of research for ME, especially given that one of the most common symptoms is headaches/migraines which could stem from such a waste build-up - not to mention that sleep is often disrupted hence not allowing for the standard 'cleaning' of the brain during sleep.

    With regard to orthostatic intolerance, I think it stems from a combination of cardiovascular insufficiency as well as autonomic - that being both sympathetic and parasympathetic - dysfunction. These systems are components of the peripheral nervous system therefore I have to question whether lack of oxygen to the brain is a central cause however given the aforementioned glymphatic system, I think damage in this way could potentially explain certain elements of orthostatic intolerance. There is no doubt that the comorbidity of ME and orthostatic intolerance ought to be telling us something is not working as intended in the circulatory and/or nervous system - both topics I intend to explore in future articles. As with everything further research is vital! Thanks for the good questions and I hope these answers give you interesting things to research and postulate on.
    aimossy likes this.
  12. 5150

    5150 Senior Member

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    Mitochondriae don't "just fail", such as by genetically. Given my 100% certainty that this disease is contagious, it's the stealth pathogen that has so far escaped identification, that is the true causal agent. I don't know the scientific process of "why" the mitochondria are damaged and don't function properly, but it is reasonable that it's associated with the invading pathogen. My best guess: it's a yet undiscovered retrovirus, very difficult to find. But it wreaks havoc by "going viral" ; hence the millions of people now infected, and many more to come if this snail's pace of research isn't sped up. We old-timers are starting to lose the ultimate battle more and more.
  13. Legendrew

    Legendrew Content team

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    I honestly think the evidence just isn't there for either ME being contagious or a 'stealth pathogen' as you put it. If mitochondrial dysfunction is involved then it is unlikely that such an infectious agent would effect the mitochondria, the sole purpose of a virus at the end of the day is to replicate. I discussed this at some length in my article exploring viruses and I recommend reading that article if viruses are your personal opinion of a causative mechanism - you might enjoy the content. I think that the endless search for viruses has done more harm than good for ME now.

    As I've expressed many times previously I believe ME is caused by a genetic defect which could potentially be passed through families. Upon great stress being placed on the immune system the genetic weakness leads to the ongoing diseases process whatever that may be - an analogy I liken it to is spreading petrol in a forest. The spark is the initial virus, infection or stress however once the forest is ablaze there seems little point in searching for the triggering virus which likely plays no role in the ongoing blaze. Whether this blaze is an autoimmune process or otherwise is yet to be seen but I think it's high time that another hypothesis took the lead as the viral hypothesis has proven incorrect for nearly 30 years - if there was something to find, i'm of the opinion that it would have by now.

    At the end of the day complex diseases need devious answers and viruses simply do not fit this disease process in my mind, autoimmunity may and I look forward to further research in this area.
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  14. aimossy

    aimossy Senior Member

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    Good article Andrew yet again!
    Your analogy in the above statement is very good.
    I think it is good that we have two areas of research happening. Virus/pathogen and autoimmune.
    Both areas will help to form the picture and produce biomarkers and analyse what is happening in our bodies. One area of research can end up helping or supporting another if it is quality research.
    I would love to see an article about all the top quality research that's happening right now and an analysis of how they may help support our picture and possibly tie up together.
    Not all of us can go searching the net or have the education to see how that might happen.
    I could do with that help, analysis and information.
    That could also promote more donations or spark more people to join ME organisations.
    Just a thought :)
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  15. August59

    August59 Daughters High School Graduation

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    They got another $2 million grant to study a larger cohort which is good.
  16. deboruth

    deboruth

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    Whose view is it that Myhill et al are not to be considered too seriously because of their "competing" interests? Would like to know whose view and which competing interests, as I am other wise somewhat lost and confused.
    justy and peggy-sue like this.
  17. Chris

    Chris Senior Member

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    A helpful essay--many thanks. You probably know the essay from Julia Newton's group, though the first listed author is D.E.J. Jones, "Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome", 2009. This suggests various mechanisms by which the ANS might exert control over the mitochondria--the essay does not use the word, but it seems implicit in how it defines "peripheral muscle."

    She also has a great little essay, "Home orthostatic training in chronic fatigue syndrome--a randomized, placebo-controlled feasibility study", 2010. I have been doing this for about 3 months now, and my OI is quite substantially improved, and I think slowly my fatigue is improving too--it is good stuff, and I recommend it, though take care--she talks about a "drop-zone" and you have to make sure that you won't get hurt if you pass out! This simple execise has been shown to cure neurocardiogenc syncope, but I think this was the first essay linking it to ME/CFS. Chris
  18. peggy-sue

    peggy-sue

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    I think OI might have a lot to do with lack of vasoconstriction, (ie, a smooth muscular problem) as well as low blood volume.
    aimossy and Legendrew like this.
  19. peggy-sue

    peggy-sue

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    There isn't one single symptom that cannot be accounted for by the lack of sufficient energy production in the mitochondria.

    How much further "downstream" can you get than the mitochondria? :confused:
    justy likes this.
  20. Legendrew

    Legendrew Content team

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    From a personal stance I think you're likely getting at something very important in the first quote. Many of the chemicals involved in vasoconstriction and vasodilation have numerous other roles and some influence directly mitochondrial function. As such any dysregulation in the endothelium (the layer of cells that secrete these vasoactive chemicals) could potentially influence mitochondrial function. By downstream, what I mean is that it is likely not the first step of dysfunction occurring - but that is not to say it could be a major part of the disease pathology, to use yet another analogy: If i were to go to the source of a river and pour in gallons of toxins there would be no obersevable problems at that area but downstream all the plants and fish would likely die, the problem started at the very source where i poured in the toxins but the majority of problems occurred much further downstream, you can help the ecosystem by purifying the water downstream but to solve the problem you'd have to stop the pollution at the river source and I think most diseases work like this. I plan to write a lot more in my next article regarding vasoconstriction and vasodilation, the endothelium and the cardiovascular system as a whole which will be worth a read if you're interested in that area of ME research.
    aimossy likes this.

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