1. Guest, the 'News in Brief' for the week beginning 8th August 2022 is here.
    Dismiss Notice
  2. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice

Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients (2019) Tomas, Brown, Newton, Elson

Discussion in 'ME/CFS research' started by John Mac, Mar 1, 2019.

  1. John Mac

    John Mac Senior Member (Voting Rights)

    Messages:
    585
    https://peerj.com/articles/6500.pdf
     
  2. roller*

    roller* Senior Member (Voting Rights)

    Messages:
    249
    what could this be ?
     
  3. Sid

    Sid Senior Member (Voting Rights)

    Messages:
    496
    Good news IMO. Implies that nothing is structurally wrong with the mitochondria per se. Likely to be a signalling problem telling them to slow down energy production.
     
    obeat, Barry, Cheshire and 16 others like this.
  4. John Mac

    John Mac Senior Member (Voting Rights)

    Messages:
    585
    An inverted signal perhaps?
     
    ladycatlover likes this.
  5. Andy

    Andy Committee Member

    Messages:
    17,128
    Location:
    Hampshire, UK
    For anybody's interest: Fukuda selection criteria, funded by the Medical Research Council, Action for ME, ME research UK, and the ME Association.

    Link to online version of paper, https://peerj.com/articles/6500/
     
    Last edited: Mar 1, 2019
  6. alex3619

    alex3619 Senior Member (Voting Rights)

    Messages:
    1,931
    If this is correct then it fits with quite a lot of other data. Our mitochondria are not working, but are not damaged, though this has been observed before. So, for example, the issue could still be local hypoxia, or PDH inhibition, or signalling factors, as others mentioned above.
     
  7. Sid

    Sid Senior Member (Voting Rights)

    Messages:
    496
    No idea really.
     
  8. Sean

    Sean Senior Member (Voting Rights)

    Messages:
    4,673
    Location:
    Australia
    measured using extracellular flux analysis.

    I have often wondered if the extracellular matrix is somehow involved, particularly the amorphous component.
     
  9. Forbin

    Forbin Senior Member (Voting Rights)

    Messages:
    1,555
    Location:
    USA
    Reminds me of Ron Davis' belief of there being "something" in the blood serum. Some molecule for which I think he had an upper or lower boundary on its size. If it's not present in healthy serum, I wonder if such a thing might be regarded as a sort of "poison"/"toxin" - perhaps some molecule usually confined to the gut. Just speculating.
     
    Last edited: Mar 2, 2019
  10. hinterland

    hinterland Senior Member (Voting Rights)

    Messages:
    310
    Absolutely, and a similar experiment has been repeated by Dr Karl Morten, as briefly reported by the ME Assocation, here.
     
    Hutan, ukxmrv, Sid and 11 others like this.
  11. hinterland

    hinterland Senior Member (Voting Rights)

    Messages:
    310
    So, if I understand correctly, and as others here have alluded to:

    1. The mitochondria themselves aren't broken: good. These researchers took the lid off the mitochondria and tested out the machinery and found it all to be operating normally.

    2. Yet, mitochondrial function in whole cells is *abnormal*. The researchers suggest this points towards a problem upstream of the mitochondrial respiratory chain (question: is this synonymous with 'electron transport chain'?). Would this be a problem with substrates getting into the mitochondria? The researchers specifically mention oxygen transport, but O2 saturation is normal when measured by finger pulse oximeter. So, is something blocking oxygen from getting into the mitochondrion? Something... in the blood!...
     
    Last edited: Mar 2, 2019
    ScottTriGuy, Forbin, Milo and 4 others like this.
  12. Inara

    Inara Senior Member (Voting Rights)

    Messages:
    2,734
    It doesn't have to be a "mysterious something" (although it could); something they don't see or understand (because, e.g., the nano-needle is not made for it), like different signals for example, or an altered signal which would be needed for activation of enzymes in the mitichondria. Or a protein. Or...

    Just one possible example (there are certainly more): It is known that calcium in the mitochondrion is needed to activate several enzymes and to ensure O2 consumption, which are needed for ATP production. If this calcium (signal and ions) is missing, not all enzymes are activated (like PDH), AMPK production increases and O2 consumption of the mitochondria decreases.
     
    ukxmrv, sb4, ScottTriGuy and 6 others like this.
  13. roller*

    roller* Senior Member (Voting Rights)

    Messages:
    249
    myhill, davis, morten may have seen something infectious/invading.

    would the plasmapheresis from scheibenbogen/berlin have filtered out such a thing or was this treatment supposed to do something different?
     
    ScottTriGuy likes this.
  14. alex3619

    alex3619 Senior Member (Voting Rights)

    Messages:
    1,931
    They have an idea of the molecular size and its much smaller than a virus, its in the protein range. It might not be protein though, as even things like lipopolysaccharides can be very large.

    PS However a pathogen might still be making it.
     
    Last edited: Mar 2, 2019
    merylg, ScottTriGuy, Forbin and 4 others like this.
  15. Inara

    Inara Senior Member (Voting Rights)

    Messages:
    2,734
    This treatment has an autoimmune background. If I understood and remember correctly, they selected patients with high values in the CellTrend panel, i.e. autoantibodies to certain muscarinergic and adrenergic receptors.
     
  16. Mij

    Mij Senior Member (Voting Rights)

    Messages:
    6,054
    We need to stop searching for pathogens, they've been ruled out at nauseam. We need an AMPK ME recharger at every 3km. Perhaps Ron Davies could develop one? Similar to electric car rechargers.

    upload_2019-3-2_15-21-34.png
     
    ukxmrv, Nellie, ScottTriGuy and 5 others like this.
  17. lansbergen

    lansbergen Senior Member (Voting Rights)

    Messages:
    616
    Not the one I suspect
     
    merylg, ScottTriGuy and roller* like this.
  18. rvallee

    rvallee Senior Member (Voting Rights)

    Messages:
    9,073
    Location:
    Canada
    Pathogens have definitely not been ruled out. We don't know much about the vast majority of pathogens out there and some pathogens previously thought to be harmless are being found to have possible disease-causing mechanisms in some people.

    A study published last year in Nature suspects EBV (or was it a Herpes virus?) to be a possible cause behind several major autoimmune diseases.

    Here a virus previously thought to be harmless could be a cause of encephalitis: https://www.folio.ca/u-of-a-scientists-discover-a-hidden-cause-of-encephalitis/.
    Recent research shows growing evidence for "inactive" viruses having an impact on the immune system because of free-floating RNA. The viruses aren't replicating in an active infection and could still have a disease-causing effect.

    Pathogens are far from having been ruled out. Researchers working on the microbiome find entirely new viruses and bacteria regularly, they barely need to try, there are so many of them.
     
    sb4, Pyrrhus, Inara and 9 others like this.
  19. roller*

    roller* Senior Member (Voting Rights)

    Messages:
    249
    perhaps, its not one culprit. its not aliens. its a crime scene.
    ...or like riddles in the fairy tales: "its not the gut, but its the gut".

    maybe our world view is hindering to proceed.
    perhaps, the best investigations so far came from "math" (statistics) ?
     
    Last edited: Mar 3, 2019
    ScottTriGuy likes this.
  20. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

    Messages:
    3,718
    Location:
    Australia
    That's the Nobel prize winning question, but the authors specifically mention this paper:
    https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-8-93

    Which along with the other 2 day cpet papers and related findings in exercise physiology provide clues, at least in my opinion, though I seem to be struggling to get people to look deeply at this stuff.
     
    obeat, Hutan, merylg and 4 others like this.

Share This Page