[HN Gopher] Mitochondrial signal transduction (2022)
___________________________________________________________________
Mitochondrial signal transduction (2022)
Author : breck
Score : 154 points
Date : 2024-06-23 12:15 UTC (1 days ago)
(HTM) web link (www.cell.com)
(TXT) w3m dump (www.cell.com)
| macawfish wrote:
| 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-whisperin...
| epgui wrote:
| For my masters' degree I studied extracellular free
| mitochondria and extracellular vesicles containing
| mitochondria. It's a wild world.
| breck wrote:
| 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 wrote:
| 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/
| comboy wrote:
| So what do you think about the paper?
| bilsbie wrote:
| Could we ever get mitochondria injections? Is anyone
| researching that?
| TaylorAlexander wrote:
| Sure I bet you could find someone to inject you with
| mitochondria...
| vixen99 wrote:
| 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.'
| epgui wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| Are they still recognized as part of the self or are they
| attacked by immune cells ?
| mathgeek wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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.
| EnigmaFlare wrote:
| It's an analogy, not a model. It's useless for making
| predictions or testing hypotheses. Even pretty useless for
| conveying understanding.
| Teever wrote:
| An analogy is a way of expressing a model in a highly
| compressed verbal state.
| mathgeek wrote:
| The term we're looking for is likely "analogical model"
| https://en.wikipedia.org/wiki/Analogical_models
| FrustratedMonky wrote:
| 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.
| mannykannot wrote:
| > 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-...
| FrustratedMonky wrote:
| 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?
| mannykannot wrote:
| 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.
| stefan_ wrote:
| Except sometimes you lose control and you grifters
| pretending your model is the real deal and the singularity
| is near.
| com2kid wrote:
| 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.
| kweingar wrote:
| > 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...")
| robertlagrant wrote:
| > 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.
| FrustratedMonky wrote:
| 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.
| alan-hn wrote:
| I don't see anything about them moving _between_ cells in that
| article. Would you mind pointing it out in case I missed it?
| macawfish wrote:
| 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.or
| g/wiki/Horizontal_transfer_of_mitocho...
|
| And also this: https://www.sciencedirect.com/science/article/
| pii/S156772491...
| moi2388 wrote:
| 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
| MilStdJunkie wrote:
| 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...
| akira2501 wrote:
| 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.
| fsloth wrote:
| "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?
| tomlue wrote:
| 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.
| WJW wrote:
| 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.
| dtech wrote:
| 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.
| akira2501 wrote:
| 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.
| jhedwards wrote:
| 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.
| acchow wrote:
| Given the billions of years of compression involved, these
| structures could occupy any number of latent spaces with all
| sorts of different meaning.
| kkoncevicius wrote:
| 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
| carrozo wrote:
| Mitochondria is the powerhouse of the cell!
|
| https://knowyourmeme.com/memes/mitochondria-is-the-powerhous...
| xanderlewis wrote:
| and a monad is a monoid in the category of endofunctors.
| proc0 wrote:
| Nah, it's a burrito.
| saghm wrote:
| A monad is a monoid in the category of endoplasmic reticulum
|
| (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!)
| level1ten wrote:
| That is addressed in the first sentence of the article.
| mathgradthrow wrote:
| mitichondrial DNA seems far too conserved to have a role as
| dynamic as "processor", but I didnt read TFA
| __loam wrote:
| Hackernews try not to make a computer analogy when talking about
| biology challenge: impossible
| kaibee wrote:
| I would like to see how biologists explain the functioning of a
| computer.
| jes5199 wrote:
| 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
| chewxy wrote:
| there's also a good paper - Can a neuroscientist understand
| a microprocessor - by Kording's lab which is also an
| excellent read.
| etiam wrote:
| ...but there's nothing more obnoxious than a physicist
| first encountering a new subject.
|
| https://xkcd.com/793/
| mynameisnoone wrote:
| It's "nerd-sniping bait" needs a more succinct metaphor.
| "Nerdbait"?
| level1ten wrote:
| > We argue that mitochondria are the processor of the cell
|
| The analogy began in the third sentence
| photochemsyn wrote:
| 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...
| mbrizic wrote:
| 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
| janpmz wrote:
| 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!
| freilanzer wrote:
| > 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?
| mpreda wrote:
| 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.
| wuschel wrote:
| Interesting - I guess there is some sort of balance there,
| given the radical biochemistry that is seen with
| Mitochondria. "The more [mitochondria] the merrier" ...?
| mrcartmeneses wrote:
| 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.
| wslh wrote:
| 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
| 1oooqooq wrote:
| 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?
| wslh wrote:
| 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.
| dekhn wrote:
| 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.
| ASalazarMX wrote:
| Wouldn't they still degrade every generation? I'd expect
| them to be created new, like new spermatozoa that are
| born with long telomeres.
| mrcartmeneses wrote:
| If that was true then how would any other single celled
| organism be able to exist?
| ASalazarMX wrote:
| Plot twist: Earth life is slowly running out of
| mitochondria.
| paulluuk wrote:
| 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?
| Steven420 wrote:
| I believe that generally when you become obese your fat cells
| are just becoming enlarged
| bbarnett wrote:
| Hey! How dare you, I resemble that remark!
| px43 wrote:
| My understanding is that only happens to a point, then new
| fat cells are generated, which will then just
| deflate/inflate when weight is lost and regained again. I
| think it's one of the reasons that losing fat is so much
| harder than gaining fat.
| UniverseHacker wrote:
| 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.
| mrcartmeneses wrote:
| They tend to concentrate in muscle cells, so fat cells
| themselves will not help much
| Symmetry wrote:
| 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.
| dumb1224 wrote:
| 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)
| charlysisto wrote:
| 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
| elric wrote:
| There are some studies that suggest that migraine might really
| be a case of mitochondrial dysfunction.
| charlysisto wrote:
| 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.
| kaibee wrote:
| > 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.
___________________________________________________________________
(page generated 2024-06-24 23:02 UTC)