Mitochondrial signal transduction (2022)(cell.com)
cell.com
Mitochondrial signal transduction (2022)
https://www.cell.com/action/showPdf?pii=S1550-4131%2822%2900459-4
117 comments
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.
I remember reading a kids science section in the Sunday newspaper that explained the internet like our circulatory system, but instead of moving blood around it moved information around. (This was mid 90s)
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.
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.
It's also interesting because there are so many analogies you could use, off the top of my head I would say the cooling loop in car would be a much less "strained" analogy even if it's still very reductive.
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.
nobody is suggesting the brain runs an instruction set or a compiler - but it does compute in a general sense.
It's an analogy, not a model. It's useless for making predictions or testing hypotheses. Even pretty useless for conveying understanding.
The term we're looking for is likely "analogical model" https://en.wikipedia.org/wiki/Analogical_models
Tomato/Potato.
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.
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.
> Do you have some solution to this age old conundrum?
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-...
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-...
A thoughtful and reasonable response.
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?
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?
Aside from the absurd title SciAm republished it under, the article originally appeared here:
https://www.nature.com/articles/nature.2014.16131
Whether it is actually much use in understanding black holes is a matter of opinion.
Whether it is actually much use in understanding black holes is a matter of opinion.
Got it.
Nice.
So you are talking about taking this concept of 'analogies' to the extreme of an actual physical 'analogy' that can be studied. Here acoustics, to mimic the event horizon (i'm simplifying).
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?
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?
I'm not thinking of anything as formal as that, more in terms of trying to get a handle on the difference between the words in ordinary language.
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...
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...
Yes, this is good article showing the downsides of analogies. Thank You.
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."
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."
> 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.
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.
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.
An analogy is a way of expressing a model in a highly compressed verbal state.
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).
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?
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?
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.
Except sometimes you lose control and you grifters pretending your model is the real deal and the singularity is near.
sublinear(3)
Metaphors help communicate ideas. I think everyone knows they are imperfect. Nobody thinks because we say the brain is a 'computer' that there are chips in there.
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.
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.
> It wasn't that long ago that we considered the brain and a computer to also be quite similar
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...")
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...")
> are all basically computers, because it flatters the egos of computer programmers
And here you are thinking tech people are all basically egomaniacs. I wonder why.
And here you are thinking tech people are all basically egomaniacs. I wonder why.
I don't see anything about them moving between cells in that article. Would you mind pointing it out in case I missed it?
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_mitocho...
And also this: https://www.sciencedirect.com/science/article/pii/S156772491...
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...
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
For my masters’ degree I studied extracellular free mitochondria and extracellular vesicles containing mitochondria. It’s a wild world.
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!
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!
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/
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/
Could we ever get mitochondria injections? Is anyone researching that?
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/ This paper refers to '61 mitochondrial modulators which are able to protect the mitochondria from toxic insults and/or improve mitochondrial function.'
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.'
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.
I’m not saying there’s nothing to see there, but if there’s anything it’s not obvious.
Sure I bet you could find someone to inject you with mitochondria…
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.
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.
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.
Are they still recognized as part of the self or are they attacked by immune cells ?
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.
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.
So what do you think about the paper?
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-mitochond...
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...
Mitochondria are ancient bacteria that merged into the eukaryotic cell, accordinga to a theroy. They have a distinct DNA from the rest of the human body and are inherited via the mother. The amount of mitochondria can change, if you exercise more and eat less sugar, the number of mitochondria in your body grows!
> The amount of mitochondria can change, if you exercise more and eat less sugar, the number of mitochondria in your body grows!
Why is that and what effect does it have?
Why is that and what effect does it have?
Mitochondria are involved in aerobic energy production in the cell, using O2 (oxygen) and some energy substrate to produce ATP (adenosyne tri-phosphate), the "energy currency of the cell".
"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.
"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.
[deleted]
Interesting - I guess there is some sort of balance there, given the radical biochemistry that is seen with Mitochondria. “The more [mitochondria] the merrier” …?
The more the merrier, yes. I’m an amateur road cyclist and most of my training is spent in the lower heart-rate “zones” trying to train my mitochondria. The theory is that for endurance sports the key variable is your mitochondria’s capacity to use oxygen and fuel to produce ATP.
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.
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.
If I'm rowing for 20-30 minutes in a HF range of 150-160, that should fall into your parameters, right? This is a very interesting fact - I have been sedentary for a couple of years and I'm fighting a kind of fatigue. Maybe this is a way to work against the symptoms. Do you know of a way to tell if the effects are taking hold?
You’ll know! I’ve been doing a lot of “base” training over the last few months and I feel a lot faster. And my Strava data agrees
It also applies selective pressure on your population of mitochondria which can reduce the prevalence of deleterious mutations and make them more efficient on a population basis.
I also understand that mitochondria is affected by Low Level Laser Therapy (LLLT) [1][2].
[1] https://www.medcentral.com/pain/chronic/low-level-laser-ther...
[2] https://weberlasersystems.com/collections/books
[1] https://www.medcentral.com/pain/chronic/low-level-laser-ther...
[2] https://weberlasersystems.com/collections/books
that theory doesn't seem to encompass all that is know.
> 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?
> 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?
The mitochondria that mothers pass down are from a special group of cells that already existed when the mother was born and they are kept in a special, protected state that minimizes damage.
Wouldn't they still degrade every generation? I'd expect them to be created new, like new spermatozoa that are born with long telomeres.
If that was true then how would any other single celled organism be able to exist?
Plot twist: Earth life is slowly running out of mitochondria.
Could you please expand your comment for people, like me, who doesn't have a good knowledge of medicine and/or biology?
Also, are you saying that LLLT fails on its claims? If so, could you please reference some study to follow the topic.
Also, are you saying that LLLT fails on its claims? If so, could you please reference some study to follow the topic.
It reminds me of the central plot of an old game called Parasite Eve (1997). I don't know if anyone still knows it.
https://en.wikipedia.org/wiki/Parasite_Eve_(video_game)
https://en.wikipedia.org/wiki/Parasite_Eve_(video_game)
Technically, if you are obese wouldn't you have more cells, and therefore a higher total number of mitochondria?
Silly example of course, but what is the obvious benefit of having a higher number of mitochondria in your body?
Silly example of course, but what is the obvious benefit of having a higher number of mitochondria in your body?
I believe that generally when you become obese your fat cells are just becoming enlarged
The obvious benefit is having a greater ability to produce cellular energy, in principle also having the feeling and experience of having more energy. When you gain weight your overall energy expenditure does go up a lot, but not really in a useful way- you are just supporting the maintenance and physical movement of the extra weight. It’s more useful to think of energy expenditure in proportion to bodyweight.
They tend to concentrate in muscle cells, so fat cells themselves will not help much
The cellular environment is such a mess it's not a surprise that environmental changes are observed by many types of bodies within the cell. It's hard to think of it like a "processor," though, when almost all of it's messages are non specific broadcasts and not direct targeted messages.
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.
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.
"To me it seems like RNA is the processor, DNA is the RAM,..."
Is there anything resembling a von Neumann machine in the biochemistry, though?
Would Turing machine analogues be more useful?
Is there anything resembling a von Neumann machine in the biochemistry, though?
Would Turing machine analogues be more useful?
Both Turing and Von Neumann machines (and the lambda calculus by Church) were designed to be minimal implementations that were still powerful enough to be provably complete in a mathematical sense. Mother Nature is under no such constraints: she happily constructs massively parallel "computers" with millions of global variables, each being written to by every core. That human minds cannot debug such systems is not Her problem. The only constraint is if it works, and it does.
Epigenetic modifications, such as methylation, are made to DNA by specific proteins. These modifications alter the transcription process from DNA to RNA, which in turn affects protein expression. This includes the expression of the proteins responsible for epigenetic changes themselves. In essence, the proteins that modify DNA also control the expression of their own building instructions through a feedback loop.
I guess that feels a bit like a von neumann machine to me, but I'm not sure the analogy is super helpful.
I guess that feels a bit like a von neumann machine to me, but I'm not sure the analogy is super helpful.
Wouldn't RNA be the RAM and DNA be long term storage? Most of the work and "decision making" - at least in current organisms - is done by proteins.
There are many different types of RNA with different purposes. They all act in concert to produce proteins. mRNA encodes proteins, tRNA brings the proteins into transcription, rRNA actually acts as a protein itself to help drive this machine.
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.
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.
But aren't alterations confined to the epigenetic proteins found in chromatin? I may be mistaken but I thought the DNA itself stays the same while the epigenetic annotations change dynamically.
A long term storage that can also be used as a trap wire to catch pathogens.
[1]: https://en.wikipedia.org/wiki/Neutrophil_extracellular_traps
[1]: https://en.wikipedia.org/wiki/Neutrophil_extracellular_traps
Given the billions of years of compression involved, these structures could occupy any number of latent spaces with all sorts of different meaning.
There was an interesting article recently about research in bioelectricity, on how each cell is equipped with the same mechanisms of data transfer and storage as a neuron is. Definitely big if true, the implications of that are crazy:
https://www.bitsofwonder.co/p/a-revolution-in-biology
https://www.bitsofwonder.co/p/a-revolution-in-biology
Hackernews try not to make a computer analogy when talking about biology challenge: impossible
It's "nerd-sniping bait" needs a more succinct metaphor. "Nerdbait"?
[deleted]
I would like to see how biologists explain the functioning of a computer.
there’s a classic paper “Can a biologist fix a radio?” that argues that biology’s tools are insufficient to understand even relatively simple machines
there's also a good paper - Can a neuroscientist understand a microprocessor - by Kording's lab which is also an excellent read.
...but there's nothing more obnoxious than a physicist first encountering a new subject.
https://xkcd.com/793/
https://xkcd.com/793/
It's about signal transduction, the process of cells taking up a wide range of external signals, sometimes environmental, sometimes from other organelles within a body in multicellular organisms (single celled critters on the eukaryotic lineage often have many mitochondria, too). It's a very analog process, not really that digital on/off in nature (e.g. many genes aren't really turned off, they just have very slow transcription rates when the trigger isn't present).
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...
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...
Apparently they play a critical role in neurones (which can have millions of them) not only because the brain is the most energy hungry organe but also because they play numerous parts in how they work : neurotransmitter transporters and regulators, stress modulator, epigenetic "signalors"... the list goes on.
No wonder ketones can have an impact such as healing epilepsy just by the effect they have on mitochondria. It is quit a fascinating domain of research and the potential it is unravelling is huge IMHO.
- https://www.youtube.com/watch?v=Y6iJMDhLmLc
- https://www.youtube.com/watch?v=_XTOKo99Ohg
- https://www.youtube.com/watch?v=o7sftaJThk8
- https://www.youtube.com/watch?v=Y6iJMDhLmLc
- https://www.youtube.com/watch?v=_XTOKo99Ohg
- https://www.youtube.com/watch?v=o7sftaJThk8
There are some studies that suggest that migraine might really be a case of mitochondrial dysfunction.
Yes I remember Dr Bikman saying that and it make sense since it is a form of uncontrolled electrical storm in the brain analagous in that sense to epilepsy.
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.
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.
> From a strictly mechanical point of view, the brain is a syncytium. While the electrical component of a spike that invades the synapse is chemically transformed into a vesicle message, the mechanical portion of the spike is transformed and propagated into and across the synapse in a way dictated by the mechanical impedance of the local membrane, cytoskeleton, and synaptic matrix.
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.
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.
If a cell is a submarine, the mitochondrials is its crew.
mitichondrial DNA seems far too conserved to have a role as dynamic as "processor", but I didnt read TFA
Mitochondria is the powerhouse of the cell!
https://knowyourmeme.com/memes/mitochondria-is-the-powerhous...
https://knowyourmeme.com/memes/mitochondria-is-the-powerhous...
That is addressed in the first sentence of the article.
and a monad is a monoid in the category of endofunctors.
https://www.quantamagazine.org/social-mitochondria-whisperin...