Benjamin Thompson
Welcome back to the Nature Podcast, this week: researchers discover that mitochondria come in more than one type…
Emily Bates
…and how smashing together atomic nuclei can reveal their shapes. I'm Emily Bates.
Benjamin Thompson
And I’m Benjamin Thompson.
Benjamin Thompson
First up on the show this week, reporter Nick Petrić Howe is here with a rather surprising finding…
Nick Petrić Howe
We all learnt about mitochondria at school — they’re sometimes described as the powerhouse of the cell and they’re extremely well studied. But it turns out that everybody may have missed something, because it seems that mitochondria actually come in two different kinds.
Craig Thompson
We were as surprised as everyone that there would be this mechanism of mitochondria to become specialised sub populations.
Nick Petrić Howe
This is Craig Thompson, a metabolism researcher who’s publishing this odd finding in this week’s Nature. He’s found that in certain situations, mitochondria will divide into specialised types that are responsible for different tasks. Now, mitochondria are best known for producing ATP, the molecule that provides the energy that drives biochemical processes. But over the last few decades it’s become clear that they are also involved in a second function — making key components for the cell to grow and thrive.
Craig Thompson
Mitochondria are essential for other things, and that is synthetic reactions that build the building blocks of proteins and lipids that allow us to engage in cell division and cell repair.
Nick Petrić Howe
Their ability to do these two things makes sense when there are plenty of resources around. But they can still do both when resources are limited, like if a cell is damaged, which has had researchers scratching their heads.
Craig Thompson
That was impossible to explain. How does the mitochondria balance the need to keep making ATP to keep the function of the cell, and at the same time produce the molecules necessary to engage in wound repair?
Nick Petrić Howe
This has been difficult to explain as there is only a finite amount of resources available. So there’s a fork in the road for the mitochondria, with the same starting resources, what end-product do they decide to make?
Craig Thompson
Once the mitochondria is limited for the nutrients with which to make ATP or to engage in synthesis of molecules as precursors. It's got to choose whether it burns it to CO2 and water, that allows you to make ATP, or it takes those molecules and use them as building blocks to build things.
Nick Petrić Howe
So, to figure out how mitochondria could make their ATP and building blocks at the same time. Craig and the team took cells and starved them of resources. When they did so, they found that the mitochondria were separating into two very different subpopulations. One of these was expert in making ATP.
Craig Thompson
So the mitochondria that are enriched in ATP synthesis become the perfect mitochondria that you want to put on a textbook to explain how mitochondria are an energy factory. They have highly ordered cristae. They're really efficient at making the super complexes that allow you to make ATP.
Nick Petrić Howe
These mitochondria were enriched in the machinery to make ATP and the cristae — the finger-like folds of mitochondria’s inner membrane that play a crucial role in making the ATP — looked like a textbook diagram. The other subpopulation looked quite different.
Craig Thompson
The other population, actually still has the double membrane of a classic mitochondria, but it's filled with filaments of proteins.
Nick Petrić Howe
These mitochondria almost looked empty by comparison, as they lacked the cristae mitochondria are famous for, and instead they contained long bundles of protein filaments. So in times of strife, mitochondria will specialise becoming physically and metabolically quite different. And it turns out a protein encoded by a specific gene plays a key role.
Craig Thompson
There was one linchpin protein that was necessary to make the judgement between these two pathways. That gene has a terrible name. It's called pyrroline-5-carboxylate synthase.
Nick Petrić Howe
This protein is an enzyme involved in making the cellular building blocks. What Craig and the team discovered was that the mitochondria essentially shuffled things between them as they separated into the two different populations. Now, mitochondria often will fuse together or split into two to repair themselves, but it seems that when they come together and then split in times of nutrient stress, this protein with a terrible name, pyrroline-5-carboxylate synthase, ended up in one population of mitochondria that became great at making important molecules, while the others, became more like the classical mitochondria we all know and love. And Craig believes the fact that these two types of mitochondria exist may help explain how some cancers can grow so rapidly, even in quite hostile conditions.
Craig Thompson
And what we show in the paper in pancreatic ductal adenocarcinoma, one of the most severe cancers, as they grow, the tumour cells acquire the segregated mitochondria that allows them to maintain their growth.
Nick Petrić Howe
Now, linking this strange mitochondrial behaviour and cancer will need more work, which Craig and the team are pursuing. It’s also unclear what drives this process of mitochondrial separation, as it’s unknown what the signals are that the mitochondria, or the cell, receive to start off the process? And how do the building-block-making mitochondria lose their famous cristae? Craig and the team speculate it might be to do with the loss of a particular part of a protein complex involved in their formation, but that complex also is important for the double membranes that both the subpopulations have. Clearly more questions remain, but for now, this work explain how mitochondria can keep cells functioning even when resources are limited. And Craig thinks there’s likely much more to uncover about how these little powerhouses that we all learn about in school, juggle competing workloads.
Craig Thompson
We're hoping, as we go through understanding when this occurs under physiologic conditions, it'll explain a lot of the unknown mysteries of how ATP production is linked to cellular processes that require ATP but also require making proteins, say the secretion of protein by various cell types either as hormones or other kinds of things.
Nick Petrić Howe
That was Craig Thompson from Memorial Sloan Kettering Cancer Center, in the US. For more on that story, and for a video where we show how these different kinds of mitochondria look, check out the show notes for some links.
Benjamin Thompson
That was Craig Thompson from Memorial Sloan Kettering Cancer Center in the US. For more on that story and for a video taking a look at these different kinds of mitochondria. Check out the show notes for some links.
Emily Bates
Coming up, a smashing way to look at the shape of atomic nuclei. Right now though, it’s time for the Research Highlights, with Dan Fox.
Dan Fox
Naked mole rats might not be pretty, but they're extraordinarily long lived, and it seems they know how to keep their genome tidy. About half of a mammal's genome consists of retrotransposons, virus-like genetic sequences that insert copies of themselves into new places in the genome. To understand the evolutionary history of these elements, researchers investigated the inactive by-products of retrotransposon activity, called ‘processed pseudogenes’ in the genomes of a wide variety of mammals. In each species, the researchers measured the number of mutations these processed pseudogenes had accrued. And because mutations accumulate over time, they could use this to estimate retrotransposon activity during specific periods. They found that most mammalian species accumulated processed pseudogenes throughout their evolutionary history. The only exception was the naked mole rat. They seemed to have stopped accumulating these inactive by-products several million years ago, indicating a long period during which retro transposon activity was suppressed. The researchers say this stability could help to explain naked mole rats extraordinary longevity. Read that research in full in Proceedings of the National Academy of Sciences of the United States of America.
Dan Fox
The midlife crisis may be one of the most consistently observed patterns in the social sciences. But new research suggests this slump may not be a universal phenomenon. A raft of previous surveys have found that well-being follows a U-shape over a person's lifetime. Happiness is high in early life, declines around one’s 40s and 50s, then rises again. But this work has tended to focus on high-income urban populations. Now, researchers have analysed life satisfaction data from people living in rural communities in Latin America, Asia and Africa. Although some showed evidence of a midlife slump, most people reported a decline in wellbeing after middle age, rather than during it. Factors associated with better wellbeing included being free of disability and living in a supportive community. The researchers hope that learning why people's emotions change during the aging process can help scientists to improve the well-being of older people. You can find that paper in Science Advances.
Emily Bates
Next up, physicists have developed a way to reveal the shape of atomic nuclei — by smashing them together. Now, if you’ve ever seen an atom’s nucleus in a textbook, you might expect it to be a ball of tightly packed protons and neutrons, with maybe some electrons zipping around it. It may surprise you to learn that in reality nuclei come in a whole range of shapes. In fact, a nucleus’ shape is really difficult to predict and can fluctuate over time. But that shape is super important, because many aspects of the element’s behaviour depends on it. And in a paper in Nature this week, researchers have come up with a new way to image the shape of the nucleus, one which seems to overcome some of the shortcomings of previous methods. It involves smashing nuclei together so hard that they vaporize and then studying the mess left behind. To find out more, reporter Lizzie Gibney, called up one of the authors, Jiangyong Jia. And started by asking him what researchers know already about the shapes of atomic nuclei.
Jiangyong Jia
So atomic nuclei are a collection of protons and neutrons. They are bounded by short range forces. They are short range, that means they can be easily deformed, but also the number of neutrons and protons are finite. That means quantum mechanics play a very important role. So as it turns out, the nuclei are not always spherical. Some of them are spherical, but most of them actually are deformed. They often take on an American football-like prolate shape or tangerine-like oblate shape. The properties of the nuclei, such as the position and the momentum of all the protons and neutrons within, they can also fluctuate over time, and this fluctuation is described by the nucleus quantum wave function. This wave function, which also describes the nuclear shape, is very hard to predict from theory, and instead, we need experiments.
Lizzie Gibney
So how previously have scientists then tried to study the shape? What kinds of experiments have they done?
Jiangyong Jia
One of the most popular method is so called coulomb excitation in which people basically collide the light ions with the nuclei and excite them. Then by measuring the gamma ray photos emitted while they decay back to the ground state, you can determine the shape. So this is a non-invasive, non-destructive method. The advantage is that the final state is very simple, but the disadvantage is that you do not see directly the neutrons. And also you do not see the shape directly because the reaction time is relatively long. So basically, it's like a long exposure image you're taking the shape average over time.
Lizzie Gibney
Of course, you know it feels like it's important to know about these nuclei that are just so important to matter in general. But why does the shape matter? Does it have any consequence if it's one shape or another?
Jiangyong Jia
Yeah, the shape determines the behaviour of the nucleus. They are important for a lot of practical reasons. So for example, you know the nucleus they play a very important role in determining which atoms can participate the nuclear fission and also they are important for understanding the origin of the heavy elements. So we know that the elements are made in the supernova explosion or the neutron star mergers. The rate of producing those heavy elements depends on the shape of the nuclei involved.
Lizzie Gibney
And so what did you do in your experiments? How did you go about trying to image the shape of the nucleus?
Jiangyong Jia
Yeah, our method is actually a completely new method. The idea is basically we take a snapshot of the colliding nuclei and determine its instantaneous shape. So basically, we accelerate two beam of nuclei at a very high speed and smash them in the middle of the detector. So we hit it so hard that we basically melt the nuclei into a soup of quarks and gluons. And so this hot plasma basically expand under pressure very rapidly in a way that is related to the initial shape. Eventually the plasma will cool down and freeze it out into thousands of particle that we measure in the detector. By marrying the momentum of all the particles we detected, we can actually roll back the clock to infer the shape of the nuclei. The advantage is that although the imaging method destroys the nuclei, we can take the snapshot over and over again, right, with the same type of nuclei. So that means we can sample all the possible fluctuations of the nuclear wave function, and from there we can reconstruct, you know, the original shape.
Lizzie Gibney
It's wild that you image something by completely obliterating it, but it sounds like an incredible method. And what specific nuclei were you looking at?
Jiangyong Jia
So we look at the uranium isotope, called the uranium-238 which has 92 protons and 146 neutrons. So this species, we collect the data in 2012 for entirely different purpose, but we took the opportunity to analyse data and realize our imaging method.
Lizzie Gibney
And when you use this method, what then did you find that the uranium looked like? What shape is the uranium nucleus?
Jiangyong Jia
Yeah. So as I said, we need to take a lot of snapshots, right. That's because unless the nucleus is completely spherical, each collision, you have a random orientation, and so the collision looks different from one collision to another collision. So when you have this uranium colliding, they can collide head-on or side-on, right? So they will form this hot plasma with a different shape. But we sample all possible orientations and compare the result with a collision of Gold-197, the gold is almost spherical means the collision geometry is nearly independent of the orientation. So we can compare the result obtained in the uranium collision with the result obtained in the gold collision we can infer the shape of the uranium. What we found is that uranium have this elongated shape, which we already know from the low-energy measurement. But we also learn something new. Basically, we are able to analyse this three-dimensional structure, right. If you think uranium is like American football it’s dimension in the X and Y direction are equal, but they are shorter than the dimension on the Z direction. What we found is that the dimension in the X Y direction are actually not equal, so that means all the three dimensions are different. So it's like American football being slightly squeezed on the side.
Lizzie Gibney
It's a little bit like a kind of battered, old deflated American football.
Jiangyong Jia
Exactly.
Lizzie Gibney
I mean, most of the matter in the universe is trapped inside nuclei, right. So it seems like a really fundamentally important thing to understand. But are there any kind of specific applications that you hope will come from doing these studies, like now that you have, or will soon have images of the shapes of different nuclei. What could that help with?
Jiangyong Jia
One possibility, we haven't done it, but this is one possibility, is that understanding the shape of nuclei could help the experimental search for a phenomenon called neutrinoless double beta decay, and this is the process that hypothesized could exist if the neutrino is its own anti-particle, but it has never been observed. But this is very important because it will help us to understand the neutrino mass and verify whether the neutrino is its own anti-particle. The expected rate for this decay channel depends on how similar the shapes are before and after decay. So, what we can do to help is that we can, by comparing the collisions of the parent nuclei and the collisions of the daughter nuclei, we could determine their shape difference very precisely, hence help reducing the uncertainties of the theory that are used to predict the rate of such decays.
Emily Bates
That was Jiangyong Jia from Stony Brook University, in the US. For more on that story, check out the show notes for a link to the paper and Lizzie’s news story.
Benjamin Thompson
Finally on the show, it’s time for the Briefing Chat, where we discuss a couple of articles that have been featured in the Nature Briefing. Now we heard Dan in the Research Highlights earlier talking about naked mole rats and clues to why they live so long. I've got a story that I read about in Nature that's kind of along the same lines, but this one is about one of the world's largest and oldest plants. It's a quaking aspen tree in Utah called Pando. Now DNA analysis has helped researchers to determine the age of this plant and revealed some clues about its evolutionary history.
Emily Bates
Is this one singular tree or is this a species of trees?
Benjamin Thompson
Well, this is a bit of a strange one, to be honest with you. So Pando means ‘I spread’ in Latin, and it is a tree, technically, but it's actually 47,000 stems that cover an area of 42.6 hectares in Utah's FishLake National Forest.
Emily Bates
Okay, so this is one organism that is taking up an immense area.
Benjamin Thompson
Absolutely right. So Pando is triploid, so its cells contain three copies of each chromosome rather than two, and as a result, it can't reproduce sexually and mix its DNA with other trees, and so it creates clones of itself. So yeah, technically, it is a tree, but it's also 47,000 trees supported by a vast root system that obviously is underground and spreads for a really, really long way.
Emily Bates
That's fascinating. And so what have they done to discover how old it is?
Benjamin Thompson
Well, it's evolved looking at the genomes. And although the offspring are genetically identical, they still accumulate mutations in their genomes as cells divide, and these variations provide information on how the plant changed since it first sprouted, and therefore you know how old it is and all the rest of it. Now, what's happened here is a team of researchers took roots and bark and leaves from across the clone and compared the DNA taken from them with DNA from unrelated, quaking aspen trees. And they found nearly 4000 genetic variants arose as Pando repeatedly cloned itself.
Emily Bates
And how old is Pando?
Benjamin Thompson
Well, how would old do you reckon it might be?
Emily Bates
A tree, I mean, very old, 1,000/2,000 years or I guess, no things can live longer than that, can't they? So 10,000 years old.
Benjamin Thompson
You’re getting close. So this research suggests that Pando’s age is 16,000 to 80,000 years old. Now this work isn't peer reviewed, it's a pre-print, but this does tally with other work. But also in this work then. So they've looked at, you know, the patterns of genetic mutation in the different clones, and they aren't necessarily what would be expected. And what the team found is that clones that are very close together, like 1- 15 metres distance between them shared a lot more mutations. But overall, while physically close clones did share more similar mutations than those far apart, the difference wasn't actually that much. And one of the researchers describes this 40-hectare site as a “well-mixed pot of genetic information”.
Emily Bates
And do they know what mechanism is allowing this organism to live so long?
Benjamin Thompson
That’s a great question. And, no. I think they've got some ideas. They think that maybe the triploid nature of its genome might lead to bigger cells, you know, overall, a bigger organism with better fitness. And something is clearly going on to protect the genome from harmful mutations, but what it is, is unclear. But there have been very few studies that have looked at really old clone organisms like Pando. Which, you know, up to 80,000 years, is absolutely mind blowing. It's part of and it provides an entire ecosystem. Whilst it may look like a forest of white trees, there's much more going on in this area. But it is under threat, it turns out that wild elk and deer, large populations of these are eating the young clones as they sprout. But I know the efforts are underway to try and get on top of that so hopefully it can last for another 16 to 80,000 years, perhaps even longer.
Emily Bates
Well, I've got a story that relates to something a few 100 years old, but not 10s of 1,000s of years.
Benjamin Thompson
Right.
Emily Bates
Now Ben, I'm sure you're aware of the “infinite monkey theorem”, that an infinite number of monkeys over time would eventually write the entire works of William Shakespeare.
Benjamin Thompson
That's right. It's a very sort of popular puzzle in terms of time and probability all this kind of stuff.
Emily Bates
Yeah, absolutely. And the key part of it is the infinity, right, the infinite number. But this is the finite monkey theorem. And so a group of researchers have taken the infinite monkey theorem as inspiration, and then run the numbers on whether you had a finite number of monkeys, how long it would take them to write different works, including the complete works of William Shakespeare.
Benjamin Thompson
Okay, so a finite number, you have a set pool of monkeys jabbing away at their typewriters. How long would it take then do these researchers think?
Emily Bates
Well, so let me go through some of the parameters that they put in place first, because I think it's quite important, because we're not dealing with infinite monkeys, infinite period of time. They did use chimps, or the number of chimps, rather than monkeys. So they're actually looking at apes here. So the population of chimps on Earth is around 200,000 and they've decided, if we take a chimps lifespan to be 30 years, and they spend every second of every day on a keyboard with 30 keys.
Benjamin Thompson
Okay.
Emily Bates
Which is all the letters in the English language, plus some for punctuation and spaces. So if 200,000 chimps continue to be that population, the time it would take them to type the entire works of William Shakespeare would be longer than the “heat death” of the universe.
Benjamin Thompson
Oh.
Emily Bates
Which they have assumed to be around a googol of years. So one followed by a hundred zeros.
Benjamin Thompson
That's disappointing.
Emily Bates
It's really disappointing
Benjamin Thompson
I was hoping the chimps would get their act together and start, you know, knocking out Macbeth or something like that.
Emily Bates
No, they're not going to get to Macbeth. They have a 5% chance of writing bananas in one chimp’s lifetime. So they might be able to write the word bananas. There is a chance that within one chimp's lifetime, they will write “I chimp, therefore I am”. Things they are unlikely to write before the heat death of the universe, include Shakespeare entire works, Planet of the Apes, which is 83,000 words, and Curious George, they're not even going to get to write Curious George, which is 1,800 words.
Benjamin Thompson
Oh, those poor chimps. I mean, I do have to ask–
Emily Bates
–mm, hm–
Benjamin Thompson
–why have they figured all this out? I mean, I know that there's lots of research into, you know, things like how language develops and all this kind of stuff. What's the thrust of this? Other than, it's quite a neat thought experiment.
Emily Bates
Yeah, it's a mathematical problem. If you look at the actual paper, there's some wonderful equations in there for what is just chimps typing words. But what they do mention in the paper at the end is they don't bring up the philosophical aspect of whether a work created by a monkey is the same as a work created by Shakespeare, who was cognizant as he was writing it. And they draw parallels between the current issue around generative AI and things being created versus human work. So yes, they have concluded that Shakespeare himself actually provided the quote as to whether monkey labour or chimp labour could meaningfully be a replacement for humans. Comes from Hamlet, act three, scene three, line 87. “No.”
Benjamin Thompson
We have to leave that there, I think, for this week's Briefing Chat. And listeners, for more on those stories or where you can sign up to the Nature Briefing to get more of them delivered directly to your inbox, check out the show notes for some links.
Emily Bates
That’s all for this week, as always you can keep in touch with us on X, we’re @NaturePodcast, or you can send an email to [email protected]. I’m Emily Bates.
Benjamin Thompson
And I’m Benjamin Thompson. Thanks for listening.
