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Inflammation turns mitochondria into toxic factorie

Discussion in 'Other Health News and Research' started by natasa778, Nov 23, 2016.

  1. natasa778

    natasa778 Senior Member

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    http://www.medicalnewstoday.com/articles/313090.php
     
    ljimbo423, Mary, Jennifer J and 25 others like this.
  2. hixxy

    hixxy Senior Member

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    Original paper:

    Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages

    Mills EL, Kelly B, Logan A, Costa AS, Varma M, Bryant CE, Tourlomousis P, Däbritz JH, Gottlieb E, Latorre I, Corr SC, McManus G, Ryan D, Jacobs HT, Szibor M, Xavier RJ, Braun T, Frezza C, Murphy MP, O'Neill LA.

    Abstract
    Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production. RNA sequencing reveals that this combination induces a pro-inflammatory gene expression profile, while an inhibitor of succinate oxidation, dimethyl malonate (DMM), promotes an anti-inflammatory outcome. Blocking ROS production with rotenone by uncoupling mitochondria or by expressing the alternative oxidase (AOX) inhibits this inflammatory phenotype, with AOX protecting mice from LPS lethality. The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state.

    Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

    KEYWORDS:
    immunometabolism; innate immunity; macrophage; reverse electron transport; succinate; succinate dehydrogenase; toll-like receptors

    https://www.ncbi.nlm.nih.gov/pubmed/27667687
    http://www.cell.com/cell/fulltext/S0092-8674(16)31162-X
     
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  3. taniaaust1

    taniaaust1 Senior Member

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    I wonder if that shift could be responsible for that "feeling poisoned" feel which sometimes can suddenly kick in with us. This could be such a major breakthrough for us
     
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  4. Paralee

    Paralee Senior Member

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    Macrophages come from the monocytes that are one of the WBC's right?

    I have had high monocytes for a long time, I know that's not right but dr after dr says that it's perfectly acceptable. I wish they'd take a ride in my body for just one day.
     
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  5. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    argentina
    excellent finding... establishes a bridge between immune and metabolic-mitochondria anomalies found of ME, which I'm sure do exist
     
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  6. natasa778

    natasa778 Senior Member

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    This may or may not be relevant to rituximab effects in ME, but still interesting:

    Rituximab therapy in refractory macrophage activation syndrome secondary to systemic lupus
    erythematosus


    Article is behind a paywall, no abstract. Here some bits:

     
    lauluce likes this.
  7. hixxy

    hixxy Senior Member

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  8. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    the connection you made might very well be right... we deactivate the macrophages and the mitochondria can breathe again... I wonder how will the full book of ME look 100 years from now... I think this is analogous to the full book of our solar system (i'm interested in space exploration). 50 years from now, that book could show a solar system with a few extra Neptune sized planets on the far reaches of the system, many earth sized ones, and even one brown dwarf (failed star), we know so little yet...
     
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  9. natasa778

    natasa778 Senior Member

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  10. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    argentina
  11. HowToEscape?

    HowToEscape? Senior Member

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    "50 years from now, that book could show a solar system with a few extra Neptune sized planets on the far reaches of the system...."

    That is rather unlikely, as we have telescopes based on land, in orbit around Earth AND on roving, space-traveling explorer craft which have reached the outer parts of our solar system. Any object as massive as a brown dwarf would affect the orbits of planets in the solar system, and its position could thus be calculated.
     
    Last edited: Nov 25, 2016
  12. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    well, it's very hard to cover the whole solar system, which expands to the oort cloud, half a light year away from the sun using current remote sensing technologies and probes. We might know a lot about the inner solar system but that's just a very little part of hte whole thing. Besides, since recently, there is very strong evidence for a ninth neptune size planet disrupting kuiper belt objects and other celestial bodies, look here: http://www.sciencemag.org/news/2016...eptune-sized-planet-lurks-unseen-solar-system
    Regarding the futility of space exploration, even I who would give everithing I have for a single treatment for ME, think it is important. There're many things with "no practical benefit" that are useful for us humans, like games, sports, music, plastic arts, cloth designing, works of fiction, etc... We can just abandon everything not related to physical preservation, I think
     
  13. HowToEscape?

    HowToEscape? Senior Member

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    I absolutely agree that some of humanity's most important pursuits are things that one can't buy, sell, eat or have otherwise "practical" benefit from. Cultures that valued only practical things stayed frozen. Even the Roman aqueducts and tunnels would not have been possible without Greek science and maths. I didn't mean at all to declare space exploration futile or un-neccesary. I've edited my previous post to remove such implication.
    That's the first I've heard about a possible unknown planet, interesting.
     
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  14. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    Sorry, maybe I misunderstood you since I'm not a native english speaker :)
    If I remember correctly, the suggestion that there might be much more in the solar system due to perturbation in other bodies started with the discovery of Sedna, which has a very anomalous orbit. It is considered too in the calculation of this planet X orbit
     
  15. HowToEscape?

    HowToEscape? Senior Member

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    Well, with brain fog etc I don't write very clearly. Nothing wrong with your English. I also didn't know about Sedna, that's interesting. I s'pose this brain fog thing means there's quite a bit I don't know about.
     
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  16. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    argentina
    Oh, we all know so little... I wished I could have go to college... :(
     
  17. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    I just received the results of a blood test showing increased monocytes too, the normal range is 8% maximum and I got 19%. In previous blood works done over the years, they always were at the high limit, 8%, 9%, even 13%, but never 19%, this is happening for the first time.
     
  18. Mary

    Mary Senior Member

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    When I have felt poisoned in the past (it hasn't happened for awhile), it's invariably connected to some form of detoxing or toxic overload so I literally am being poisoned. I never feel poisoned with plain old PEM.
     
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  19. lauluce

    lauluce as long as you manage to stay alive, there's hope

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    I feel the same, when I feel poisoned, I think I am actually poisoned!
     
    Mary likes this.

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