16 ms·
Mitochondrial signal transduction (2022)
- blurbleblurble 2y agoFrom 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 agoFor my masters’ degree I studied extracellular free mitochondria and extracellular vesicles containing mitochondria. It’s a wild world.
- breck 2y agoVery 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 agoWet 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 agoSo what do you think about the paper?
- bilsbie 2y agoCould we ever get mitochondria injections? Is anyone researching that?
- TaylorAlexander 2y agoSure I bet you could find someone to inject you with mitochondria…
- vixen99 2y agoI 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 agoThat 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 agoIt 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 agoCalling 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 agoAre they still recognized as part of the self or are they attacked by immune cells ?
- epgui 2y agoI 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 agoThe 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 agoit'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 agoEverything 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 agoIt 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 agoIt'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 agoI 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 agoAh 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 agoNot 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 agoSome 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...
- akira2501 2y agoThe 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 2y ago"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 2y agoEpigenetic 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 2y agoBoth 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 2y agoWouldn'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.
- carrozo 2y agoMitochondria is the powerhouse of the cell! https://knowyourmeme.com/memes/mitochondria-is-the-powerhouse-of-the-cell https://knowyourmeme.com/memes/mitochondria-is-the-powerhous...
- xanderlewis 2y agoand a monad is a monoid in the category of endofunctors.
- proc0 2y agoNah, it's a burrito.
- saghm 2y agoA 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!)
- tpoacher 2y agoThey rely on Functors, which are transcribed at the ribosome!
- level1ten 2y agoThat is addressed in the first sentence of the article.
- mathgradthrow 2y agomitichondrial DNA seems far too conserved to have a role as dynamic as "processor", but I didnt read TFA
- __loam 2y agoHackernews try not to make a computer analogy when talking about biology challenge: impossible
- kaibee 2y agoI would like to see how biologists explain the functioning of a computer.
- jes5199 2y agothere’s a classic paper “Can a biologist fix a radio?” that argues that biology’s tools are insufficient to understand even relatively simple machines
- mynameisnoone 2y agoIt's "nerd-sniping bait" needs a more succinct metaphor. "Nerdbait"?
- deleted 2y ago[deleted]
- photochemsyn 2y agoIt'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/Beyond-ATP-new-roles-of-mitochondria https://portlandpress.com/biochemist/article/44/4/2/231672/B...
- mbrizic 2y agoThere 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
- janpmz 2y agoMitochondria 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 2y ago> 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 2y agoMitochondria 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.
- deleted 2y ago[deleted]
- wuschel 2y agoInteresting - I guess there is some sort of balance there, given the radical biochemistry that is seen with Mitochondria. “The more [mitochondria] the merrier” …?
- mrcartmeneses 2y agoThe 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.
- charlysisto 2y agoApparently 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=Y6iJMDhLmLc - https://www.youtube.com/watch?v=_XTOKo99Ohg https://www.youtube.com/watch?v=_XTOKo99Ohg - https://www.youtube.com/watch?v=o7sftaJThk8 https://www.youtube.com/watch?v=o7sftaJThk8
- elric 2y agoThere are some studies that suggest that migraine might really be a case of mitochondrial dysfunction.
- charlysisto 2y agoYes 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 2y ago> 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.
- deterministic 2y agoIf a cell is a submarine, the mitochondrials is its crew.