Mitochondrial signal transduction (2022)
cell.com
cell.com
https://www.quantamagazine.org/social-mitochondria-whisperin...
A decade+ later I randomly picked up a Sunday paper and they were explaining the circulatory system "as if it was a computer network, but instead of moving data around, it moves blood around".
I thought it was funny that going from 95 to 2005, the expectation for innate understanding of biology vs digital technology had flipped.
nobody is suggesting the brain runs an instruction set or a compiler - but it does compute in a general sense.
One mans analogy is another mans model.
Do you have some solution to this age old conundrum? How are we to use language to describe new things without using any existing words?
Of course, just make up new words is one solution. But for a lot of things, that gets to also be confusing, and not help communicate an idea.
Well, as it happens, the person you are replying to did have at least an outline of a solution in this case, which could be stated thus: analogies may be regarded as models to the extent that they are useful for making predictions or testing hypotheses. it probably needs some refinement (for example, analogies carefully-crafted to "predict" the outcome in very narrow cases, but which diverge significantly with modest changes, probably don't count), but it is about as good as you can get in pinning down the semantics of ordinary language.
For example, a hydraulic analogy to electric circuits may be useful in simple cases, but once reactive elements are introduced, it is probably time to abandon it. Similarly, the 'bowling-ball on a mattress' analogy for general relativity cannot even predict the precession of Mercury, while some hydraulic and acoustic models have, apparently, been useful for better understanding black holes (even though they also spawned ridiculous headlines like "Scientists Close in on Creating Black Hole in Lab."[1])
In the case of TFA, I personally feel that the analogy being pushed is at best useless and probably misleading for any purpose.
[1] https://www.scientificamerican.com/article/scientists-close-...
Especially like bringing up the hydraulic example.
I was reacting to a common trope on HN to react harshly to any type of metaphor about the brain.
When, where is the outrage when describing 'voltage' as a type of 'water pressure in a hose'. As you say, it is only accurate to a degree.
Like giving a presentation on 'cloud' computing, and the power point has clouds, and some cohort of IT people are seething in the back of the room, "those aren't really clouds, they are servers".
Guess that is the problem, all analogies are only accurate to some degree, or else they would be the original. Nothing can be fully explained by something else, without both models being the same. So at some point, analogies are just helpful to communicate some concepts, but are not complete.
Yet, having something 'similar' can help get over some hump in understanding the 'new thing'.
That link is pay walled, do you have another copy?
Whether it is actually much use in understanding black holes is a matter of opinion.
This is pretty extreme case. I was just saying generally, that metaphors and analogies can help explain concepts. This is finding actual real correspondence between different 'model's.
Were you saying earlier that there was a way to model this correspondence between models generally, for other cases? Maybe there is a category theory or something, to relate different models, so they can be analogies of each other, but both real so can have experiments?
Metaphors, analogies and models often help us understand things, but they can mislead unless they are, to a reasonable degree, models of the thing we we are trying to understand. The physicist Matt Strassler calls the latter 'phibs', and has written a recently-published book motivated by one in particular, an attempt to explain the relevance of the Higgs field. https://profmattstrassler.com/2024/04/16/why-the-higgs-field...
Interesting that while critiquing the common analogy, it did suggest another one. I wonder if the problem isn't analogies, it is just finding 'good ones'.
"As an analogue, consider air pressure (which is itself an example of an ordinary field.) Air is a substance; it is made of molecules, and has density and weight. But air’s pressure is not a thing; it is a property of air, , and is not itself a substance. Pressure has no density or weight, and is not made from anything. It just tells you what the molecules of air are doing.
The Higgs field is much more like air pressure than it is like air itself. It simply is not a substance, despite what the phib suggests."
I was a bit sloppy in distinguishing model and analogy. I guess I meant physical analogy like pressure/voltage (which does outrage me!) vs model being an abstract description of the phenomenon built from the ground up, and was thinking in the context of physics or engineering.
The problem with the "bad" kind of analogies/models is they come with a list of conditions under which they don't apply, which is huge and usually not specified at all. For the "good" kind (Ohm's law/etc.), they come with a list of conditions under which they do apply which is finite and explicitly stated along with the equations so you can actually know if the model correctly describes a particular case.
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?
On other hand, scientist/philosophers that attempt to makeup 'new' words just to avoid this, sometimes make it worse and their ideas become even more obfuscated.
Many people in tech still think this. It will take a while to dislodge the idea that if you squint enough, cells, brains, etc. are all basically computers, because it flatters the egos of computer programmers.
There are genuine connections between specific biological systems and certain ideas in computer science, but most of the casual analogies you hear from tech people only serve to inflate their own perceived authority ("I know a lot about computers, and cells/brains are like computers, so here is my take about cells/brains...")
And here you are thinking tech people are all basically egomaniacs. I wonder why.
I'd assumed "between" was about this: https://en.wikipedia.org/wiki/Horizontal_transfer_of_mitocho...
And also this: https://www.sciencedirect.com/science/article/pii/S156772491...
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!
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/
Mitochondrial Modulators: The Defender 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.'
I’m not saying there’s nothing to see there, but if there’s anything it’s not obvious.
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.
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.
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-mitochond...
Why is that and what effect does it have?
"exercise more" means "higher energy needs", and growing the amount of mitochondria would be adaptive.
"eat less sugar" means less anaerobic energy production, I guess. Thus more aerobic energy production in exchange.
Further, if the mitochondria is being asked to make more ATP than it can aerobically, then it will skip the final respiratory step and respire without oxygen (anaerobically). This causes a build up of lactate in the cells that is not tolerated above a certain level, I believe due to it raising acidity levels in the cell.
You’ll often hear athletes and coaches talk about lactate threshold and Functional Threshold Power (FTP). This is all to do with mitochondria function.
[1] https://www.medcentral.com/pain/chronic/low-level-laser-ther...
> Wallace notes: “The mitochondrial theory of aging holds that as we live and produce ATP, our mitochondria generate oxygen free radicals that inexorably attack our mitochondria and mutate our mitochondrial DNA.”1
if aging is killing the mitochondria, why then the mother passing mitochondria to the offspring give them a blank state if they got dna-damaged mitochondria to begin with?
Also, are you saying that LLLT fails on its claims? If so, could you please reference some study to follow the topic.
Silly example of course, but what is the obvious benefit of having a higher number of mitochondria in your body?
To me it seems like RNA is the processor, DNA is the RAM, and mitochondria are voltage regulation modules. That they're all environmentally sensitive is a consequence of how the machine is constructed.
Is there anything resembling a von Neumann machine in the biochemistry, though?
Would Turing machine analogues be more useful?
I guess that feels a bit like a von neumann machine to me, but I'm not sure the analogy is super helpful.
DNA is environmentally sensitive and it can be altered. Your entire genome is not being produced all the time. Different proteins are copied based upon the conformal structure of DNA which changes based upon the cellular environment. The entire structure is copied often and no one particular set of DNA in your body is "the original."
It has aspects of long term storage but then it's utilized in a way that long term storage almost never is. And all cells get their own copy which may be unique in several ways. So RAM seems like a better metaphor to me.
[1]: https://en.wikipedia.org/wiki/Neutrophil_extracellular_traps
The references in the paper have some more general information, this one looks good for a broader overview of the history of mitochondrial research:
https://portlandpress.com/biochemist/article/44/4/2/231672/B...
- https://www.youtube.com/watch?v=Y6iJMDhLmLc
The main theoretical idea behind mitochondrial dysfunction is that it is a root cause of many mental health issues : depression, bipolar syndrome, migraine, alzheimer (aka type 3 diabete)... even schizophrenia. And the reason given is you have those neurone networks with impaired mitiochondria that are over or under excitable. These are not dead neurone so it is reversible if you can bring back healthy mitochondria... Part of it is done through mitophagy and mitogenesis induced by fasting/ keto therapy.
I always hear that the brain doesn't do back-propagation the way that NNs are trained, but why are we so sure of that? This reads to me like a potential communication channel for doing backprop.
https://knowyourmeme.com/memes/mitochondria-is-the-powerhous...
(I've made this joke before, but I've never had a chance to in a context where both parts of the malapropism are relevant!)