Mitochondria as you've never seen them | Hacker News Reader

Mitochondria as you've never seen them

nature.com

343 pointsBrajeshwar87 comments

I studied an BSc in genetics and none of our lectures or textbooks presented mitochondria any differently from the classic bean shape they introduce in school. This is surely old news to folks who specialise in mitochondria, but it's easy to miss out on these fundamentals even if you've studied in a relevant area at degree level, because there's just so much to know in biology.

In fact, it's one of those fields where the more you learn, the more you realise we'll never reach a satisfactory understanding in our lifetime. You could chuck an endless supply of PhD students at every constituent domain for generations and still feel like you've scarcely scratched the surface of the many things there are to question.

> You could chuck an endless supply of PhD students at every constituent domain for generations and still feel like you've scarcely scratched the surface of the many things there are to question.

Sounds like a much better use of tax dollars than some other uses!

> the more you realise we'll never reach a satisfactory understanding in our lifetime

Depends on how long you intend to live, really

> Depends on how long you intend to live, really

https://slatestarcodex.com/2017/11/09/ars-longa-vita-brevis/

Thanks for sharing. That was a great story.

And thank you for posting the thank you because it was that that prompted me to bother to follow the link. I too think it was a great story, well told.

What books did Caesar read? In reality, books are not that useful. History doesn't show too much accumulation of knowledge over time - there is virtually no continuity between the bronze age and classical antiquity. Almost everything was lost, and built anew. Then it was all lost in another dark age. A few scraps remained.

In fact, civilisation rises and falls as brainpower rises and falls. There only was a long period of rise recently, but, it's been long over, and we now live off the scraps of what it produced.

Caesar almost certainly read classics of Greek philosophy and Roman literature.

But what does your comment have to do with books? There were none in the Bronze Age, nor for many centuries after it.

I was commenting on the absurdity of the story. It just doesn't seem to be how knowledge works. Nothing was discovered by such slow, long term accumulation of knowledge. Instead, knowledge seems to be discovered very quickly when the potential is there, and it decays and gets forgotten if the potential is lost.

For example, it was perfectly possible to be born when there was no powered flight at all, and live to see the moon landing. And, while there are all the plans, and everything there was to write down about Saturn V, we can't do it again, as the human potential isn't there anymore. In fact, we can't even fly supersonic anymore.

We certainly know how to do both those things (and military planes fly supersonic daily). That's because it's written down.

I think it's now a historical fact that we in fact don't, as it's now virtually certain that the Artemis program, with all that knowledge available, will at the very least take longer to send people to the Moon, than the Apollo program did with no prior knowledge at all.

Somebody once claimed that the problem isn't that Johnny can't read, or that Johnny can't think, but that Johnny doesn't even know what thinking is, which is certainly a correct observation, but he incorrectly blamed it on the American schooling system.

But Johnny doesn't know what thinking is the same way that somebody who was born blind doesn't know what seeing is. You don't have to be taught to think, you just do. You figure things out, then you learn that others also know them. Or, sometimes that they don't, and know something completely different about the thing for whatever weird reason.

And such a person can live their entire life without thinking, convinced that being smart is simply about learning more and faster, and if they study hard, they will understand the topic on that deeper level like the old masters did, and perhaps they will also contribute something new one day.

But the thinking never comes.

We can make the butt of a rocket with 27% more payload capacity than Saturn V fall out of the sky and slot itself into giant mechanical pincers. More than twice the capacity if you forgo the catch.

The human potential is there.

By one possible definition, this is the difference between science and everything else like medicine or engineering: science prioritizes advancing knowledge above all else, so (in a system not distorted by publication metrics) that means it prioritizes transmitting and in particular saving it.

Engineering does not—because of commerce, engineering can often even be actively hostile to transmitting knowledge. (I have a person next to me who knows how enterprise SSDs work and refuses to tell me more than “with great difficulty and ingenuity”.) Even without that, the task is difficult enough that without an explicit pressure to refine and preserve explanations that just won’t happen. There always will be people who value and enjoy that, but without a system in place to cultivate and reward them, there won’t arise that a kind of “collective knowledge” akin to collective immunity (or percolation) that the gaps can filled in.

This is actually a problem in the more engineering-oriented parts of science as well. For example, this is one of the problems with Hossenfelder’s suggestion that we stop building colliders: if we do that, in ten to fifteen years (a couple of generations of grad students) it’s fairly certain that we won’t be able to build them on anything like the current level. The US has already experienced this kind of institutional knowledge loss, in fact, with the shuttering of the SSC. So while I agree that they haven’t produced new—not just knowledge, but understanding in quite a while, we need to be really really sure before agreeing to lose this expertise.

And yet, look at physics. Like take a quantum field theory course (taken by what, probably a thousand, ten thousand students per year?) and trace the dependency chain. Even discounting all the backround knowledge we take for granted (e.g. “electricity exists”), the dependency chain is really really deep, probably something like a decade if you count the requisite high-school parts. (It includes some things that might seem unrelated on first glance but are in fact essential, like optics and thermodynamics.) That creates an actual problem in teaching it. And the subject itself is a year to two years deep at least before it becomes wide enough that you can mix and match topics, to say nothing of actual research.

I shudder to think what would happen if you tried to work through all of the materials science you encounter in an average first-world home (and all of the materials science, metallurgy, chemistry required to build that, etc.). An extremely fun project to contemplate, but I suspect too long for a human lifetime.

Fortunately, biology is broad but not particularly deep, so even undergrads routinely contribute to research. The story is a much better analogy for fundamental theoretical physics. Source: got some background in both, decided it didn't make sense to do theoretical physics before longevity is solved.

I'm reading an excellent book right now called Cells, Embryos and Evolution, in which one topic is the exploratory nature of certain biological processes. One of the processes described is the dynamic instability of microtubule growth.

Microtubules randomly grow and shrink from an anchor in the cell until they hit something that stabilizes them. Through their random growth they explore the cell, which means that processes depending on microtubules are robust against changes in size and shape of both the containing cell and the target object that needs the microtubules. The author explains that we still don't know how microtubules are stabilized, which I thought was fascinating.

Except that the book was written twenty years ago, and now we DO know how they are stabilized. It turns out that the author was the person who discovered microtubule instability, and since then we have not only figured out what stabilizes them, but have developed numerous cancer drugs based on those molecules: https://www.ncbi.nlm.nih.gov/books/NBK9932/#_A1831_

The progress of science is really incredible.

Have we made much progress in understanding how the Kinetochore works?

Not in genetics, but the kind of cursory neuroscience education that "AI" courses contain often goes no further than a sample cell at one point in the first weeks. I have found that the majority of AI graduates believe each cell contains one Mitochondria, even those who can explain the chemical processes behind associative memory and understand how there are multiple binding sites/receptors in most of those processes.

It goes to show how much simple diagrams influence understanding. The synaptic gap diagrams show multiple receptors and abstracted neurotransmitters, and gradients of multiple Ca or K ions. The neuron diagram shows one Mitochondria. That start influences their understanding for years.

> This is surely old news to folks who specialise in mitochondria

from Wiktionary:

> mitochondrion, Coined in German by Carl Benda in 1898, from Ancient Greek μίτος (mítos, “thread”) + χονδρίον (khondríon), diminutive of χόνδρος (khóndros, “grain, morsel”)

from Wikipedia article on Carl Benda:

> In an 1898 experiment using crystal violet as a specific stain, Benda first became aware of the existence of hundreds of these tiny bodies in the cytoplasm of eukaryotic cells and assumed that they reinforced the cell structure. Because of their tendency to form long chains, he coined the name mitochondria ("thread granules").

So yeah, I guess this is known ever since mitochondria was first discovered, definitely "old news". I can't understand why it is always depicted as bean-shaped.

> I can't understand why it is always depicted as bean-shaped.

Do you disagree with the reason suggested in the article?

I have a BS in neurobiology from 2005 and the one lesson I took away and has been reinforced over and over again for me is that we know very little about biology. For example, epigenetics was only just getting talked about when I graduated. We are still only scratching the surface.

Mitochondria are a descendant of early bacteria which infiltrated an Archaea cell, traded genes, and started replicating with it, forming a new organism about 1.5bn years ago.

The wild part is that all mitochondria are descended from that single event.

This was a rather controversial theory called Endosymbiosis and it was pioneered by Lynn Margulis. Now it is widely accepted.

https://evolution.berkeley.edu/it-takes-teamwork-how-endosym...

The controvesial part is hypothesising nerve cells are endosymbiotically adapted fungus, and such like.

Because there was some skepticism in the thread about this theory, I emailed one of the top scholars in this area to get his up to date perspective and he delivered this amazing response:

"I'll be happy to give you a succinct summary of my views on this issue.

Molecular evidence (notably DNA sequence) absolutely confirms that the mitochondrial genome is of bacterial origin. The most compelling evidence in this regard comes from the sequence of the mitochondrial DNA (mtDNA) in a group of protists (eukaryotic, mostly single-celled, microbes) called jakobids. Key publications presenting the evidence and the arguments are:

Lang BF, Burger G, O'Kelly CJ, Cedergren R, Golding GB, Lemieux C, Sankoff D, Turmel M, Gray MW. 1997. An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature 387:493-497. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&d...

Burger G, Gray MW, Forget L, Lang BF. 2013. Strikingly bacteria-like and gene-rich mitochondrial genomes throughout jakobid protists. Genome Biol. Evol. 5:418-438. http://gbe.oxfordjournals.org/content/5/2/418.abstract

While sequence data firmly support the endosymbiont hypothesis insofar as the mitochondrial genome is concerned, the data also support the conclusion that the mitochondrion originated only once:

Gray MW, Burger G, Lang BF. 1999. Mitochondrial evolution. Science 283:1476-1481. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&d...

Of course, only a few essential mitochondrial proteins are encoded in mtDNA and synthesized inside mitochondria. The vast majority of the 2000+ proteins that make up a mitochondrion are encoded in the nuclear genome, synthesized in the cytoplasm, and imported into mitochondria. So, when we speak about the origin of the mitochondrion, we have to account not only for the mitochondrial genome (which is unquestionably of bacterial origin) as well as the mitochondrial proteome: the collection of proteins that constitute the complete organelle.

Accepting that the mitochondrion originated as a captive bacterium or bacteria-like entity, massive evolutionary restructuring has evidently occurred in the transition from endosymbiont to integrated organelle, including endosymbiotic gene transfer (movement of genes from the endosymbiont genome to the nuclear genome, with loss of the mtDNA copies), recruitment of host proteins, and acquisition of new proteins from outside the host via lateral gene transfer from other organisms. A very complicated business, made even more complicated by the recognition that subsequent mitochondrial evolution has taken different pathways in certain respects in different eukaryotic lineages.

While the CONCEPT of the endosymbiont hypothesis, as outlined above, is strongly supported and accepted, HOW this might have happened is still unclear, and may never be settled to everyone's satisfaction. Did the mitochondrion emerge early in the evolution of the eukaryotic cell through the union, by an unspecified mechanism, of a primitive archaeon (host) and primitive bacterium (endosymbiont), with this union actually being instrumental in the emergence of the eukaryotic cell? Or, did the mitochondrion emerge late, in an evolving archaeon host that already had some of the hallmarks of a typical eukaryotic cell, notably phagocytosis, the well-known mechanism by which modern eukaryotic cells take up bacteria for food? The pros and cons of these two (and many other) scenarios are still being hotly debated.

Hope this helps.

Cheers,

Michael W. Gray, PhD, LLD (h.c.), FRSC

Professor Emeritus

Department of Biochemistry and Molecular Biology

Dalhousie University

Halifax, Nova Scotia B3H 4R2, Canada."

Does anyone here have a sense of what time frame the video covers? Like, is that real-time and mitochondria are continuously mildly active? Is it vastly slowed down and mitochondria are ripping around in our cells like madmen? Is it vastly sped up and mitochondria are actually relatively static, slow movers?

Looking around, here's a post by the author on Twitter where he shows similar motion and states that the time-lapse is 10m at 1min/sec.

https://x.com/mag2art/status/1385940103189745669

I'd guess it's a few minutes (5-10) compressed into the 10s video

Mitochondria are so absurdly more complex and interesting than what is mostly taught in schools. Awesome video!

Really sucks that antibiotics, especially bacteriocidal ones, appear to target mitochondria as if they were bacteria. This mistargetting causes sometimes severe and long-lasting side effects.

They are (ancient) bacteria

So each of our cells is a habitat for a network of wiggly energy-producing worms...

So it's fair to say that I'm pretty much worms that walk.

HP would be absolutely thrilled to know that. Or maybe terrified out of his mind. One of the two for sure.

It's wormy things all the way down.

In the Halo universe, the "Hunter" enemy, the hulking shitheads covered in armor and blasting you with a fuel rod cannon and you have to shoot their orange weak spots, are actually colonies of little orange worms!

Also IIRC they work in pairs because they are mates. When you fight them you are killing a couple.

more like wiggly other cells, which are essential as one of our main energy systems. It's funny when you dig into these, the terms are things like fermentation[0]... say what? My body is producing beer for energy?

[0] https://en.wikipedia.org/wiki/Fermentation

Well mitochondria are important for cellular respiration where oxygen IS available, yeah?

Are these wiggly other cells… a habitat for a network of wiggly other cells?

Even the Wikipedia entry on them has the classic bean-shaped diagram. If they are not really like that, why did that become the standard representation? Have they always been know to exist in more network-like structures, and was that why there was initial resistance to seeing their origin in free-living prokaryotes?

It was because they could only image a dead/fixed 2D cross section on an electron microscope. The 2D cross section of a vast interconnected network of tubes looks like disconnected small “beans.”

Cell diagrams are simplifications. Cells are not like your room with a few things inside. They are more like a decent city. In human cells you have hundreds to thousands of mitochondria.

It came from NIH/NIGMS public archive: https://images.nigms.nih.gov/pages/DetailPage.aspx?imageid2=...

Wow! Really shows how mitochondria are actually just bacterial cells living inside us!

It's called symbiogenesis, for the record https://en.wikipedia.org/wiki/Symbiogenesis

This might be a sign of different schools of thought on the matter, but I'd alwys seen it referred to as endosymbiosis (as your article also notes).

Mitochondria are in endosymbiosis with eucaryotic cells. Symbiogenesis is the idea that eucaryotes came into being ("genesis") because some prior lifeforms joined in endosymbiosis.

> the idea that eucaryotes came into being ("genesis") because some prior lifeforms joined in endosymbiosis is the theory of symbiogenesis

Nope, endosymbiosis refers to the theory per se [1]. The 1966 article that "renewed interest in the long-dormant endosymbiont hypothesis of organelle origins" [2] referred to "the idea that the eukaryotic cell arose by a series of endosymbioses" [3]. The term symbiogenesis "was first introduced by the Russian Konstantin Sergeivich Mereschkovsky" in 1910.

Hypothesis: the school split is an artefact of symbiogenesis (the original term) being revisited during the Cold War. (It also seems symbiogenesis refers to the broader biological phenomenon of symbiosis. There was a symbiogenesis of the Nemo-anemone relationship. Nemo is not endosymbiotic to anemones.)

[1] https://evolution.berkeley.edu/it-takes-teamwork-how-endosym...

[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC5426843/

[3] https://www.sciencedirect.com/science/article/pii/S002251931...

This photograph was of a bone cancer cell.

I had heard that cancer (in general) suppressed mitochondria in preference for anaerobic respiration, and that apoptosis commonly involves these organelles.

Not this cancer cell, it would seem.

You're most likely talking about Warburg effect[1].

[1]: https://en.wikipedia.org/wiki/Warburg_effect_(oncology)

> Powerhouses of the cell

Will we ever get away from this cliche? I loathe it because it's not only a cliche but I don't believe it actually helps the lay person understand the role of mitochondria. It's not completely inaccurate since they're effectively refining energy substrates (fat, glucose) into ATP by converting ADP in the TCA cycle; ATP becomes ADP again from energy expenditure and the cycle repeats, to oversimplify things. Are we adequately teaching people that mitochondria don't create or release (utilizable) energy? I kind of doubt it. But maybe I'm just annoyed from hearing that descriptor a bajillion times starting from middle school.

> mitochondria don't create or release (utilizable) energy?

I'm confused: Where do my muscles (cross-bridge cycle) get the ATP from if not from mitochondria?

I don't know, you make it sound like a pretty good analogy to me.

A coal power plant take a form stored energy which is relatively difficult to use because it has to be burnt with oxygen producing harmful waste products, and turns that energy into electricity which is easier to use in a variety of applications.

A mitochondria take a form of energy which is relatively difficult to use, sugars and fats, because they must be respired with oxygen producing harmful waste products, and turns that energy into ATP which is easier to use in a variety of applications.

This makes me want to further explore the similarities in form and function of mitochondrial networks and mycelial networks.

So beautiful and so sad to think about how much more interesting biology is than what we can teach from textbooks.

Ain't that the truth.

For instance: Before following Kurzgesagt - In a Nutshell and purchasing Mr. Philipp Dettmer's amazing book called Immune, i had never even heard of the complement system.

I found Immune a drag. Really enjoyed Cells At Work though!

The first two seasons were awesome, but i didn't like the Code Black spinoff that much.

Why is it sad, and why are we restricted to textbooks still?

To think I've spent hours upon hours each week for years and year with the express goal of producing more of these in the muscle cells of my legs, and I call this novel goal "exercise".

Madeline L'Engle was right all along

Professor Burnette makes videos and other things. Very cool stuff.

https://x.com/MAG2ART

Mitchondria may also help us keep time: https://www.quantamagazine.org/what-makes-life-tick-mitochon...

May help our cells keep time. The article doesn’t suggest that they’re the mechanism for consciousness awareness of time.

In the video, the mitochondria appeared to be motile. Are they?

Without this symbiotic relationship in cellular life on other planets, would it prevent complex cellular life?

No, there’s multiple options. Our biology is based on endless optimization of one of them not the only possibility.

All life we know of originates from one type of single-cellular life, the last universal common ancestor (LUCA)

https://en.wikipedia.org/wiki/Last_universal_common_ancestor

Which is unsurprising as any original self replicating organisms that showed up significantly later would be at a massive disadvantage, and early competition had billions of years to find a winner.

It’s worth remembering that evolution can end get stuck in suboptimal solutions because they still beat 99.999…% of the possibilities. Our blindspot is an issue but it showed up early enough that there’s been vast amounts of optimization based around that initial slightly sub optional feature.

Exhibit b.

Getting cancer, or specifically short telomeres, is a suboptimal evolutionary outcome that other some other mammals don’t have

But because the issue appears after we reproduce, it passes on

I love the Roman Bath photos!

The Seven Daughters of Eve are alive and well, I see

I want to see the frame data and rendering code.

Is the link supposed to go to a slideshow?

Yeah, the page is weird. The actual content is only on the second "block"; a video of the mitochondria under a confocal microscope.

The better title might be the second part: "January’s best science images"

This is incredible

By coincidence, today's xkcd comic matches this topic perfectly! https://xkcd.com/3046/

is the "old family tradition" punchline less small-audience than I'd have feared? eg https://en.wikipedia.org/wiki/Stromatolite#/media/File:Strom...

https://pubmed.ncbi.nlm.nih.gov/32989265

There are shockingly few images of mitochondria available online.

I started a project to increase that number by 1,000,000x: https://powerhouse.breckyunits.com/

I'm currently mastering the same confocal fluorescence technique used in this image (but borrowing microscope time, as the scope costs >$250K), but also developing an at-home protocol using Janus Green that should cost less than $200.

hey I've something to say, this reply I'm making is not related to the parent. i'm kind of disappointed you "tried" colider by looking at the syntax. Not mad just sad, makes sense that I didn't add build instructions when your video was recorded.

thx.

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