5 ms·

From one machine analogy to the another... Mitochondria have been observed moving between cells. These are living organisms! Reducing their role to that of "mic

From one machine analogy to the another... Mitochondria have been observed moving between cells. These are living organisms! Reducing their role to that of "microprocessor" seems suffocating. https://www.quantamagazine.org/social-mitochondria-whispering-between-cells-influence-health-20210706/ https://www.quantamagazine.org/social-mitochondria-whisperin...

epgui 2y ago
For my masters’ degree I studied extracellular free mitochondria and extracellular vesicles containing mitochondria. It’s a wild world.
- breck 2y ago
  Very interesting. Can you tell more? What was that like? What was your day to day? Wet lab/dry lab, etc? What % are extracellular? Did you study mitoribosomes at all? No detail is too small!
  - epgui 2y ago
    Wet lab. It was horrible. 6 years of dishwashing and monotony. I write software now and am much happier. The numbers were very difficult to reproduce and sensitive to tiny variations in experimental conditions, to the point of mystery. My MSc took me 6 years rather than 2, and that’s with a >90% scope cut. I can say that there was a “comparable” proportion of freeMitos to mitoMPs in the samples I was studying, which were induced from 786-O and 786-O/VHL cell cultures using a variety of agonists (atypically low concentrations of A23187, compared to literature, and serum-starved cell culture medium, seemed to work best; usual concentrations of A23187 seemed very violent on the cells, which is relevant if you’re trying to ascertain anything about physiologic conditions). Shockingly, a very sizeable proportion (10-50% of EVs above a certain detection threshold, probably near 100-150nm) of total EVs were either mitoMPs or freeMitos. I did not study mitoribosomes. I was trying to optimize conditions for the generation of EVs (literature is lacking here), enrichment of samples, and flow cytometric techniques for measuring EV subpopulations. Mitochondria make everything much more complicated and even gum up the tubes, requiring special care. Experiments that measure EVs without controlling for the presence of mitochondria are IMO inherently suspect. Their prevalence will depend on sample types, but from what I’ve seen, I believe the default assumption should be that they are present in relevant amounts. I’ve observed similar subpopulations in other cell lines, but with fewer controls and validations (I was focused on 786-O cells). There is a really great paper published by L Boudreau in the journal Blood with better results than anything I ever achieved, it’s very interesting stuff: https://pubmed.ncbi.nlm.nih.gov/25082876/ https://pubmed.ncbi.nlm.nih.gov/25082876/
- comboy 2y ago
  So what do you think about the paper?
- bilsbie 2y ago
  Could we ever get mitochondria injections? Is anyone researching that?
  - TaylorAlexander 2y ago
    Sure I bet you could find someone to inject you with mitochondria…
  - vixen99 2y ago
    I don't know about that but mitochondria can and are modulated by a variety of factors and of course, they include dietary components. Mitochondrial Modulators: The Defender https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953029/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953029/ This paper refers to '61 mitochondrial modulators which are able to protect the mitochondria from toxic insults and/or improve mitochondrial function.'
  - epgui 2y ago
    That sounds rather dangerous. Free mitochondria provoke quite intense inflammatory reactions. I’m not saying there’s nothing to see there, but if there’s anything it’s not obvious.
- inglor_cz 2y ago
  It is my impression that extracellular vesicles are now considered to be one of the prime suspects in the aging process, including its potential reversibility.
  - epgui 2y ago
    Calling them a “prime suspect” is both true and the wrong way around. They are ubiquitous and necessary to maintain normal physiological conditions / normal function, across all cell types and in all systems. This is the reason why we are discovering that they play important roles in pathology: it’s because they’re an important part of the machinery, and things can go wrong with any part of machinery.
- agumonkey 2y ago
  Are they still recognized as part of the self or are they attacked by immune cells ?
  - epgui 2y ago
    I would say yes to both questions, in some sense. In many ways, they don't merely get attacked by immune cells, but also participate in immune function (and pathology). At the same time, intracellular components found outside the cell, generally, tend to activate the innate immune system, in a similar way that foreign bodies do.
mathgeek 2y ago
The idea of comparing evolved structures to the current height of technology is usually an oversimplification. It's amusing to think back to when the switchboard was compared to the brain, for example. It wasn't that long ago that we considered the brain and a computer to also be quite similar, but we know it's only in certain aspects.
- exe34 2y ago
  it's called a model. all models are wrong but some are useful. the plugboard model of the brain was useful in the sense it suggested pieces working together and functional connections varying for different activities. nobody is suggesting the brain runs an instruction set or a compiler - but it does compute in a general sense.
  - soloist11 2y ago
    Everything computes in a general sense, even atoms. But one could just as easily say everything is "just" mathematics because all models of reality are mathematical. In general I think it's important to be wary of totalizing ontologies and metaphysics of reality that reduce everything to a single universal substance (monadology) or activity like computation (computationalism).
    - robertlagrant 2y ago
      It doesn't seem that important, unless you can say why in this case it's important. This seems to be saying "mitochondria aren't only the powerhouse of the cell - they also do computation." What's to be wary of in this case?
      - soloist11 2y ago
        It's a vacuous statement. All physical systems are computers because the logic of computationalism is circular. Everything is a computer so there is no meaning in the statement and the danger is that as more people start believing in the circular logic of computationalism they'll be more willing to delegate their cognition to computers even in cases where they should not, e.g. social media and algorithmic feeds designed to increase engagement and profits for advertisers.
alan-hn 2y ago
I don't see anything about them moving between cells in that article. Would you mind pointing it out in case I missed it?
- blurbleblurble 2y ago
  Ah you're right. I misread "between" in the opening paragraphs of this article and admittedly pasted the link before fully reading the article oops :D I'd assumed "between" was about this: https://en.wikipedia.org/wiki/Horizontal_transfer_of_mitochondria https://en.wikipedia.org/wiki/Horizontal_transfer_of_mitocho... And also this: https://www.sciencedirect.com/science/article/pii/S1567724918301983 https://www.sciencedirect.com/science/article/pii/S156772491...
- moi2388 2y ago
  Not in that article, yet there are studies that claim they can move between cells: https://www.pnas.org/doi/full/10.1073/pnas.0510511103 https://www.pnas.org/doi/full/10.1073/pnas.0510511103
MilStdJunkie 2y ago
Some years ago, one of those "Consciousness Studies" or "Intelligence Studies" people unveiled a new model for thinking about the brain: as an "ant farm" for mitochondria. The notion being that ant colonies work as large scale organisms, and can do some pretty complicated stuff. Well, the bigger notion is that the brain, viewed holistically, really does look like an ant farm when it's in action. I wish I could find the cite . . . oh here we go https://inference-review.com/article/the-excitable-mitochondria https://inference-review.com/article/the-excitable-mitochond...

epgui 2y ago

For my masters’ degree I studied extracellular free mitochondria and extracellular vesicles containing mitochondria. It’s a wild world.

breck 2y ago
Very interesting. Can you tell more? What was that like? What was your day to day? Wet lab/dry lab, etc? What % are extracellular? Did you study mitoribosomes at all? No detail is too small!
- epgui 2y ago
  Wet lab. It was horrible. 6 years of dishwashing and monotony. I write software now and am much happier. The numbers were very difficult to reproduce and sensitive to tiny variations in experimental conditions, to the point of mystery. My MSc took me 6 years rather than 2, and that’s with a >90% scope cut. I can say that there was a “comparable” proportion of freeMitos to mitoMPs in the samples I was studying, which were induced from 786-O and 786-O/VHL cell cultures using a variety of agonists (atypically low concentrations of A23187, compared to literature, and serum-starved cell culture medium, seemed to work best; usual concentrations of A23187 seemed very violent on the cells, which is relevant if you’re trying to ascertain anything about physiologic conditions). Shockingly, a very sizeable proportion (10-50% of EVs above a certain detection threshold, probably near 100-150nm) of total EVs were either mitoMPs or freeMitos. I did not study mitoribosomes. I was trying to optimize conditions for the generation of EVs (literature is lacking here), enrichment of samples, and flow cytometric techniques for measuring EV subpopulations. Mitochondria make everything much more complicated and even gum up the tubes, requiring special care. Experiments that measure EVs without controlling for the presence of mitochondria are IMO inherently suspect. Their prevalence will depend on sample types, but from what I’ve seen, I believe the default assumption should be that they are present in relevant amounts. I’ve observed similar subpopulations in other cell lines, but with fewer controls and validations (I was focused on 786-O cells). There is a really great paper published by L Boudreau in the journal Blood with better results than anything I ever achieved, it’s very interesting stuff: https://pubmed.ncbi.nlm.nih.gov/25082876/ https://pubmed.ncbi.nlm.nih.gov/25082876/
comboy 2y ago
So what do you think about the paper?
bilsbie 2y ago
Could we ever get mitochondria injections? Is anyone researching that?
- TaylorAlexander 2y ago
  Sure I bet you could find someone to inject you with mitochondria…
- vixen99 2y ago
  I don't know about that but mitochondria can and are modulated by a variety of factors and of course, they include dietary components. Mitochondrial Modulators: The Defender https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953029/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953029/ This paper refers to '61 mitochondrial modulators which are able to protect the mitochondria from toxic insults and/or improve mitochondrial function.'
- epgui 2y ago
  That sounds rather dangerous. Free mitochondria provoke quite intense inflammatory reactions. I’m not saying there’s nothing to see there, but if there’s anything it’s not obvious.
inglor_cz 2y ago
It is my impression that extracellular vesicles are now considered to be one of the prime suspects in the aging process, including its potential reversibility.
- epgui 2y ago
  Calling them a “prime suspect” is both true and the wrong way around. They are ubiquitous and necessary to maintain normal physiological conditions / normal function, across all cell types and in all systems. This is the reason why we are discovering that they play important roles in pathology: it’s because they’re an important part of the machinery, and things can go wrong with any part of machinery.
agumonkey 2y ago
Are they still recognized as part of the self or are they attacked by immune cells ?
- epgui 2y ago
  I would say yes to both questions, in some sense. In many ways, they don't merely get attacked by immune cells, but also participate in immune function (and pathology). At the same time, intracellular components found outside the cell, generally, tend to activate the innate immune system, in a similar way that foreign bodies do.

mathgeek 2y ago

The idea of comparing evolved structures to the current height of technology is usually an oversimplification. It's amusing to think back to when the switchboard was compared to the brain, for example. It wasn't that long ago that we considered the brain and a computer to also be quite similar, but we know it's only in certain aspects.

exe34 2y ago
it's called a model. all models are wrong but some are useful. the plugboard model of the brain was useful in the sense it suggested pieces working together and functional connections varying for different activities. nobody is suggesting the brain runs an instruction set or a compiler - but it does compute in a general sense.
- soloist11 2y ago
  Everything computes in a general sense, even atoms. But one could just as easily say everything is "just" mathematics because all models of reality are mathematical. In general I think it's important to be wary of totalizing ontologies and metaphysics of reality that reduce everything to a single universal substance (monadology) or activity like computation (computationalism).
  - robertlagrant 2y ago
    It doesn't seem that important, unless you can say why in this case it's important. This seems to be saying "mitochondria aren't only the powerhouse of the cell - they also do computation." What's to be wary of in this case?
    - soloist11 2y ago
      It's a vacuous statement. All physical systems are computers because the logic of computationalism is circular. Everything is a computer so there is no meaning in the statement and the danger is that as more people start believing in the circular logic of computationalism they'll be more willing to delegate their cognition to computers even in cases where they should not, e.g. social media and algorithmic feeds designed to increase engagement and profits for advertisers.

alan-hn 2y ago

I don't see anything about them moving between cells in that article. Would you mind pointing it out in case I missed it?

blurbleblurble 2y ago
Ah you're right. I misread "between" in the opening paragraphs of this article and admittedly pasted the link before fully reading the article oops :D I'd assumed "between" was about this: https://en.wikipedia.org/wiki/Horizontal_transfer_of_mitochondria https://en.wikipedia.org/wiki/Horizontal_transfer_of_mitocho... And also this: https://www.sciencedirect.com/science/article/pii/S1567724918301983 https://www.sciencedirect.com/science/article/pii/S156772491...
moi2388 2y ago
Not in that article, yet there are studies that claim they can move between cells: https://www.pnas.org/doi/full/10.1073/pnas.0510511103 https://www.pnas.org/doi/full/10.1073/pnas.0510511103

MilStdJunkie 2y ago

Some years ago, one of those "Consciousness Studies" or "Intelligence Studies" people unveiled a new model for thinking about the brain: as an "ant farm" for mitochondria. The notion being that ant colonies work as large scale organisms, and can do some pretty complicated stuff. Well, the bigger notion is that the brain, viewed holistically, really does look like an ant farm when it's in action. I wish I could find the cite . . . oh here we go https://inference-review.com/article/the-excitable-mitochondria https://inference-review.com/article/the-excitable-mitochond...