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Cargo-Loading of Misfolded Proteins into Extracellular Vesicles: The Role of J Proteins, 2018, Pink et al.

Discussion in 'Other health news and research' started by wastwater, Dec 17, 2019.

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  1. wastwater

    wastwater Senior Member (Voting Rights)

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    Last edited: Dec 18, 2019
    wastwater, Dec 17, 2019
    #1
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  2. alex3619

    alex3619 Senior Member (Voting Rights)

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    Proper folding of proteins requires reduced glutathione. Oxidative stress or glutathione deficiency (including potentially cofactor depletion like lipoic acid) make this a big issue. I have been talking about possible misfolded mitochondrial proteins for decades now. The total amount of the proteins can be normal or even high, but how much is working?
     
    alex3619, Dec 17, 2019
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  3. Midnattsol

    Midnattsol Moderator Staff Member

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    But oxidative stress would surely affect other proteins as well as the mitochondrial ones? It does not discriminate.
     
    Midnattsol, Dec 17, 2019
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  4. Wonko

    Wonko Senior Member (Voting Rights)

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    Surely it would 'discriminate' in that components that are more active would be affected more?

    I don't know but it might be that mitochondria would be one of the more active components of a cell?
     
    Wonko, Dec 17, 2019
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  5. Midnattsol

    Midnattsol Moderator Staff Member

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    I'm not sure level of activity changes how a protein will be affected by free radicals. Fatty acids (unsaturated ones are most prone to this) are not enzymatically active for example, but can still be oxidized, because of their chemical properties. Mitochondrial membranes could be affected before their proteins, it depends on how stable the proteins are (I have no idea about the stability of mitochondrial proteins).

    Though, mitochondria not functioning property can produce free radicals and their own proteins would be in close proximity. The same with their membranes.
     
    Midnattsol, Dec 17, 2019
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  6. alex3619

    alex3619 Senior Member (Voting Rights)

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    Yes, but the highest concentration of oxidative stress as free radicals would be inside the mitochondria.

    Furthermore, these proteins are folded INSIDE the mitochondria, so that a lack of reduced glutathione, induced by oxidative stress, means a lack of folding. This is not the same as free radical damage to the proteins.
     
    alex3619, Dec 18, 2019
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  7. wastwater

    wastwater Senior Member (Voting Rights)

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    I was thinking a lack of heat shock proteins may cause this
     
    wastwater, Dec 18, 2019
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  8. Midnattsol

    Midnattsol Moderator Staff Member

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    Sorry I've just been through exam season and my mental fatigue is adding up. When you are talking about folding and reducing environments, do you mean how it affects disulfide bridges in the protein? A lack of reduced glutathione > oxidized cysteines and formation of disulfide bonds? I'm not familiar with reduced glutathione in regards to protein formation. Please tell me more, my protein structure class was not very in-depth and I've come to realize how little chemistry I've had in cell biology and biochemistry previously :p

    They could change protein folding, yes. But if the premise is that protein levels has been measured this should've been picked up? There are at least one or two old studies that has looked at heat shock proteins. I wish someone else would pick up on this.
     
    Midnattsol, Dec 18, 2019
    #8
  9. alex3619

    alex3619 Senior Member (Voting Rights)

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    Yes.
     
    alex3619, Dec 18, 2019
    #9
  10. Midnattsol

    Midnattsol Moderator Staff Member

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    Some proteins need the disulfide bridges created in an oxidative environment, though. So saying that correct folding of proteins (like in "all proteins") requires reduced glutathione feels like a stretch to me, although it's not my area.

    Reading about "mitochondrial Precursor Over-accumulation Stress" mPOS now, not exactly what you are referring to I think, but one pathway is misfolding of intermembrane mitochondrial proteins. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851816/
     
    Midnattsol, Dec 18, 2019
    #10

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