'Turbocharged' Mitochondria Power Birds' Epic Migratory Journeys
quantamagazine.org107 points by rbanffy 3 days ago
107 points by rbanffy 3 days ago
It seems like mitochondria research is going to have a lot of impact over the next decades. For example, apparently some people with fatigue diseases have damaged mitochondria (eg, Dianna Cowern aka ThePhysicsGirl who has had a terrible long COVID illness)
I really hope so.
I went through a bout of cronic fatigue after a nose surgery that lasted ~4 months and it was utter hell. It really feels like the life has been drained from your body and on top of that, random things go wrong with your body seemingly every day. One day you’ll have strange stomach bloating and feel nauseous, another day you’ll barely be able to stand without fainting, another day you’ll feel heart palpitations, etc.
What made it so much harder to deal with was it’s an invisible illness. Nobody knows about it, and it generally doesn’t show up on tests. The only test that showed anything significant was a tilt-table test where I fainted in the middle of it.
Otherwise I went to the hospital multiple times because I thought I was having a heart attack, I’ve had doctors get angry at me for “wasting their time”, thinking I’m faking it, and friends/family not understanding.
Not to mention having to pretend everything was fine at work. There were times I had to lie down on the bathroom floor to keep myself from fainting or due to heart palpitations. Luckily we had clean, private bathrooms.
As I said, I slowly got better over the course of months, and not everyone is that lucky unfortunately. Honestly if I didn’t get better I probably wouldn’t be here to write this…
Not to trauma dump but a lot of people don’t know about these illnesses or think they’re fake so I wanted to relay my experience.
I don't want to rain on your parade but this was most likely not CFS. Chronic Fatigue Syndrome is diagnosed through the Canadian Consensus Criteria where Post Exertional Malaise is one of the defining factors. Where your body reacts to exercise or exertion 24h-48hrs later, not in the moment, but later. It also has to be going on greater than 6 months. CFS isn't "fatigue", its a bad name, it is a syndrome of symptoms.
Sounds horrible! I'm glad you recovered!
Yeah! Especially the "nose surgery that lasted ~4 months"!
But be honest: even the surgeons must have been tired after that: 4 months of looking down the same nose - Gaaaaah!
> apparently some people with fatigue diseases have damaged mitochondria (eg, Dianna Cowern aka ThePhysicsGirl who has had a terrible long COVID illness)
In these conditions it’s more likely that mitochondrial dysfunction is part of the chain of events leading to the fatigue, not necessarily the root cause of the condition.
Also I have to tread very lightly on this topic to avoid giving the wrong idea: Be a little cautious when taking statements about Long COVID and ME/CFS from individuals, as it’s not uncommon for people to present hypotheses as more concrete than the research suggests. With all due respect to Dianna Cowern, some of her past updates on the topic have blurred the lines between conjecture and fact and she’s collaborated with at least one Long COVID / ME/CFS organization that is known for having members that are sometimes less than scientific about their personal theories. It’s a very difficult and complex topic and it can be hard for patients to stay on top of all the different directions the research is looking.
Thank you for posting this :) I've have chronic fatigue for 6 years, and yeah, there's tons of uncertainty here (if there was an easy answer we would've all used it by now, lol). ME/CFS overlaps a lot with long covid, but there's also common comorbidities that further muddy the picture (MCAS, POTS, ehler-danlos syndrome, CCI, fibromyalgia, etc).
The #1 sign of ME/CFS is post-exertional malaise, which is a delayed crash after even mild exertion, with the crash arriving anywhere from 4-48 hours later, and lasts for days after. Exertion can be taking a shower, thinking hard, etc.
I just recently ruled out ME/CFS for me personally after figuring out that I don't have delayed crashes, but I still haven't figured out source of the fatigue (potentially MCAS?).
Feel free to ask any questions :)
I agree you do not have CFS.
>I still haven't figured out source of the fatigue (potentially MCAS?).
MCAS is easy to self-diagnose or at least it was in my case. Mast-cell symptoms are triggered by exercise, sun exposure, orgasms and having the connective tissue in your abdomen jiggled (e.g., by riding in a bus with bad suspension along a road with many potholes). For me it is always the same symptoms (fatigue, maybe irritability, maybe a feeling of heat on the skin) regardless of the trigger. Sometimes exposure to one of these things is not enough to trigger symptoms, but then a second exposure before the body has had time to recover from the first exposure will trigger symptoms.
Also (after you remove yourself from any triggers) if the symptoms ameliorate slowly but surely over a period of 2 to 4 hours, that is a pretty strong sign that that the symptoms were caused by mast-cell "granulation" (activation) or at least it is a strong sign in my personal case: I have other chronic conditions that can cause similar symptoms, but if one of the other conditions causes a bout of fatigue or inability to stay productive, the severity of the symptoms will increase and decrease in chaotic or unpredictable ways.
Hmm, that doesn't line up with what I've read... Dr. Afrin talks about how MCAS is a lifelong issue that only gets worse later on. Things like a history of bloody noses, strange allergic reactions (random hives or asthma), ear infections as a child, etc.
According to him, there should also be at least a couple of active symptoms, such as alternating diarrhea/constipation, edema, skin rashes or hives, foods that are high in histamine, pain while urinating, a constant feeling of being cold, hot flashes, and some others. He also encourages exercise as it helps regulate the immune system.
I certainly don't mean to invalidate your own experience—I know how hard it can be to not be understood—but perhaps there's something else that would explain it better? I'm happy to be corrected :)
MCAS is actually one of the trending diagnoses that has attracted a lot of misinformation and misdiagnosis.
Specialists who treat MCAS are overwhelmed by referrals and requests from patients who don’t meet the criteria or don’t have any basic lab work that suggests MCAS. Many of the diagnoses from primary care or self-diagnoses are from people who have been led to believe that it explains their vague symptoms. There are also a lot of people who believe they have MCAS despite negative labs, non-traditional symptoms and a non-response to medication, which is another way of saying they probably don’t have it.
So watch out. It’s trending among doctors who dabble in alternative medicine or who use it as a catch-all explanation for vague symptoms, but the social media version of MCAS has diverged from the medical definition.
Ehlers-Danlos is another self-diagnoses that is spreading in these communities. This one is so bad that actual Ehlers-Danlos specialists have difficulty sorting through referral requests because so many people and even doctors think it explains vague symptoms. It’s also trending heavily on TikTok.
CCI was briefly popular as an explanation due to a few high profile influencers. For a few years everyone was demanding imaging and sending it to one of a few doctors who specialized in it. Unfortunately those doctors were found to be excessively quick to diagnose. There were a lot of people on forums who rushed into those surgeries with no improvement at all.
Be really careful on the forums. When people start claiming they have a long list of hard to diagnose conditions (MCAS, Ehlers-Danlos, CCI, etc) all at once it’s more likely that they’ve been either self-diagnosing with each trend or they have a doctor who will confirm any vague diagnosis they suggest. These things come in waves of popularity and you can tell when some of these people joined the social media circles by their list of self-diagnoses. Sadly, so much time has been wasted on chasing dead end diagnoses that spread via social media.
Thanks for the warning :) I have responded to mast cell stabilizers and H1/H2 blockers, which is one reason I'm pursuing further treatment. I've also read Dr. Afrin's 70 page paper on MCAS diagnosis, so I have a pretty good idea of what is and isn't MCAS. And after 6 years of pursuing and failing to find treatment, I've also got fairly good at avoiding quacks...
> There are also a lot of people who believe they have MCAS despite negative labs, non-traditional symptoms and a non-response to medication
Will agree on non-response, but the typical blood test (tryptase) is not accurate in many cases[2]: "For example, in contrast to proliferative mastocytosis which usually drives significantly elevated tryptase levels, relatively non-proliferative MCAS usually presents with normal tryptase levels;"
> When people start claiming they have a long list of hard to diagnose conditions (MCAS, Ehlers-Danlos, CCI, etc)
Yes and no. [1] is a recent review that finds that these things really are quite comorbid with ME/CFS. All of them at once? Probably not, but a couple is common.
[1] https://www.medrxiv.org/content/10.1101/2024.11.27.24317656v...
[2] https://www.mastcellaction.org/assets/_/2021/09/18/b74c0e90-...
I have a thing where I can do abnormal exercise and two days later feel like a truck is hitting me slowly. is this similar? I've always just brushed it off.
Really hard to say from just that, what do you define as abnormal exercise?
Couple of thoughts:
1. PEM is triggered by things that would be fine for a normal person (walking to car, standing in a line, etc). Over exercising is definitely a thing, but it's not the same as PEM
2. Does the following fatigue cause significant impairment, and does it last for a few days?
There's some other criteria, but those are the first cut.
In these conditions it’s more likely that mitochondrial dysfunction is part of the chain of events leading to the fatigue, not necessarily the root cause of the condition.
To rephrase, it's possible she already had an underlying mitochondrial dysfunction that was not caused by COVID, but then when she caught the virus it triggered some symptomatic metabolic dysfunction that's persisting even after she cleared the virus. This kind of thing is known to happen in some people with some viral diseases, but it's poorly understood.
Mitochondria might be involved, but the impairment might be the result of some other factor.
In other words, it could be more of a symptom than a root cause.
Makes sense. To be fair, I don't think Diana claimed that that was the root cause, only that her mitochondrial function was "f'd".
It's still really interesting to me. I had really never considered the possibilities of dysfunction at this low a level at all.
> damaged mitochondria
Does that mean in all the cells or only some? Does this damage remain as cells die and get replaced by new ones? Is this damage encoded in the DNA or caused later by COVID?
What I mainly mean is, is this damage getting replicated to new cells as your body generates new ones? AFAIK only DNA affects what new copies of cells will look like, so if it's only caused by COVID later on, what keeps this persistent?
Some longevity researchers could investigate the DNA sequence of the mitochondrial DNA(a discrete object) to see if there is a length of life correlation = CRISPR edit towards longer life. It would be easily explored in mice and then there could be some edits in an egg very soon after fertilisation to replace that mitochondrial DNA in that egg to see the result. Might be a hard task to find/replace all these mitochondria and maintain life? In a single mouse egg = how many are there? A search finds this interesting paper = a good rabbit hole indeed. It is an area of intense research. https://pmc.ncbi.nlm.nih.gov/articles/PMC4684129/
We are not able to modify human mitochondria other than with TALENs or ZFNs - CRISPR doesn't work (can't import the sgRNA). Even that doesn't work that well. We have not been able to genetically transform human mitochondria. It's a big open question of how we could do it. In yeast you use a gene gun because they can actually survive it, and even that is exponentially harder than normal yeast engineering.
Hundreds to thousands of mitochondria per cell. They also encode pretty few genes, and those genes are mainly there because they directly get injected into the membranes. There are like a thousand mitochondrial genomes per nuclear genome, each with only ~10 genes that repair each other, while the nucleus has literally thousands of mitochondrial genes in two copy. Much easier to look at that
I see, your knowledge far exceeds mine in this arena. Yes, I knew they encoded few genes. Makes me wonder if they could be built in a protein shop (if even they knew how it rolled and folded in volume after editing in the longer life or higher energy genes from ?? That said, it must be highly conserved = hard job, as the conserving mechanism could resist by back editing??
They're kinda a built-in protein shop (got their own ribosomes) - but they're only for 1 thing, which is locally regulating the insertion of extremely hydrophobic proteins for respiration. You could imagine that this one application (maintaining and repairing membrane potential) requires MAXIMUM performance and response (they gotta be JIT-ed into the membrane), so much that the cell maintains thousands of genes for those ~13 genes to be able to be expressed, and it is totally worth it. Everything else gets moved to the genome. It's like we have tiny virtual machines that we can scale to respire more.
Chloroplasts are a more interesting example of a protein shop. RuBisCO, for example, the most abundant protein on earth, is coded in chloroplasts to scale expression. It is mainly there for dynamic scaling purposes, whereas the mitos are very optimized for one thing
Mitochondria don't go back because if there is 1000 mt genomes to 1 nuclear genome it is extremely energetically desirable to have 1 copy rather than 1000 copies of any given gene.
Yes, googled it. A hugely replicated one trick cowboy made to perform on cue. RuBisCo = a deep rabbithole indeed. https://www.youtube.com/results?search_query=RuBisCO Thanks, as a casual reader I appreciate explanations from someone like you!!
There are ~100,000 mitochondria in a human egg cell-- I think that's a pretty tall order.
Yes, I suspect is starts with extra metabolic capability = greater need for the task it is being prepared for. Since women have all their oocytes from an early age - speculating they might mature for fallopian release, and in that maturation mitochondrial proliferation occurs? Alternatively this might occur at puberty with hormonal triggering oocytes in some sequential manner as evolutionary efficiency might be a 'just in time' process?
It's doable https://www.nature.com/articles/s41467-022-33530-3
100,000 x 6kbp == 600 million, or less than 1/5 of our genome. Difficult part is the barcoding bits, but that is not THAT hard.
Would be interesting if there’s some trigger hormone or other mechanism that triggers turbo mode. It’ll be being used in the Tour de France in no time if so.
(FYI I’m not a biologist and have no idea what I’m talking about)
Also if this is something that is specific to the birds' mitochondria or could be triggered in mitochondria of any species.
We’ve been evolutionarily divergent for at least a hundred million years so it seems slim, but not zero.
Also don’t forget that mitochondria have their own genome and that it’s undeniable that the avian mito-dna lineage would also experience Darwinian (haha, apt) forces spurring the developments of these capabilities that our ancestors didn’t go through.
> We’ve been evolutionarily divergent for at least a hundred million years so it seems slim, but not zero.
But how much has our mitochondria differed in that time?
"With few exceptions, all animal mitochondrial genomes contain the same 37 genes: two for rRNAs, 13 for proteins and 22 for tRNAs. (...) the comparison of animal mitochondrial gene arrangements has become a very powerful means for inferring ancient evolutionary relationships, since rearrangements appear to be unique, generally rare events that are unlikely to arise independently in separate evolutionary lineages."
Source: Boore (1999) Animal mitochondrial genomes. Nucleic Acids Res. 1999 Apr 15;27(8):1767–1780
Hyperlink: https://pmc.ncbi.nlm.nih.gov/articles/PMC148383/
i.e. mtDNA changes a lot less than our "normal" cell nucleus nDNA
Fun fact: respiration is what really caused eukaryogenesis and the ability for multicellular life to occur. If archaea (what our nuclear genomes are derived from) weren't being kinda weird in the deep ocean, we would never have existed. Bacteria and archaea (other than eukaryote ancestor) have never created multicellular life. And it's because respiration. (cross posting below from my comment on another thread)
For efficient respiration, you need to have the translation/transcription of certain ATP synthase genes near to the membrane for basically JIT-ing them when ready to maintain membrane potential, and hence energy generation. Otherwise, the membrane potential falls apart. This simple need is why there are zero multicellular bacteria and multicellularity evolved 6 times in eukaryotes. By decoupling the rest of the genome from the JIT bits (ie, mitochondrial DNA), you can scale energy independently of genetic information. So if you need 1000x the energy, you need like 5% more DNA (mitochondrial DNA) instead of 1000x more DNA in your genome.
Some estimates say that our eukaryotic genes are in charge of 5000x more energy than the equivalent bacterial gene. Hence, our genomes can inflate that much and its fine. And they have. All that inflation lets us have bullshit hang around in our genome, and hey, sometimes evolution figures out something to do with all that bullshit. We evolved 1000x more complexity than bacteria because we decoupled the performance code from the rest of the code.
“We were just amazed and interested in how can these birds fly for thousands of miles without stopping, at a really high intensity, when most of us can barely run a 5K"
On the one hand, sure, it's interesting, and the article digs in and is interesting in general -- but that phrase feels off and trite, similar to saying "We were amazed that cheetahs can run over 60mph, while most humans can't manage 10mph" or "We were amazed that sperm whales can hold their breath for 90 minutes while most humans can't manage a minute"
Related:
Mitochondria Are More Than Powerhouses–They're the Motherboard of the Cell
One of the interesting findings in the article’s linked paper was that vitamin E is an effective dietary antioxidant (in birds) but only if they do 2 hours of cardio per day.
It’s interesting how “turbo” has had so much semantic drift that people don’t even know it’s a specific component in an engine. They just think it means “fast”. Wouldn’t be surprised to eventually see a “turbo” trim levels for EVs someday.
You're behind the times, turbo has drifted (heh) far in to meaning 'fast' of sorts:
- https://en.wikipedia.org/wiki/Turbo_Pascal
- https://www.specialized.com/il/en/turbo-levo-4-pro/p/4218703...
- https://turbo.hotwired.dev (Drifts right back to turbo charger, but using one as the logo)
Or it can be used to amplify as in "Turbo Clippy":
Don’t forget the turbo button, which is almost as old as turbo pascal.
I prefer the real Borland Pascal, thank you very much.
(The turbo button slowed the clock rate down for old games and some ISA cards that didn't like faster clock rates.)
I’m curious did anyone here have a turbo button that actually did speed up performance? My 386SX had a turbo button but all it did was turn on a light.
For most of us it was a misnomer because it was a lag button not a turbo button. It defaulted to on. If you turned it off it would make the machine slower, allowing certain programs to run properly instead of too fast for humans.
But we all have stories of a friend whose machine was slow because they hit the button not understanding what it does. For them it did become the turbo button.
It varied but the older ones definitely had a visible impact if you had something CPU bound running. There was an old helicopter-themed game my dad had which would start running impossibly fast because everything was based on cycle counts rather than actual time.
I was disappointed to discover that the screen scrolling in Warcraft III was too fast to make large maps usable. I was so excited to find that game used and I couldn’t play it in the early 00’s.
My 286 went from 8 MHz to 12 MHz when I hit that turbo button. And yeah that was instantly noticeable.
Kept it on except for one ninja game which was unplayable on turbo, using fixed cycle count as delay mechanism. So all enemies and movements were crazy fast on turbo.
Although that is an electric equivalent of an actual turbo car rather than just trim.
Well, the Taycan is electric only, and has a Turbo trim!
https://www.porsche.com/usa/models/taycan/taycan-models/tayc...
Haha as a car enthusiast, whenever I see "turbo" my next thought is always the inherent downside, "turbo lag" (the non-zero time it takes for the turbo to actually kick in)!
I’m a little surprised we don’t have mild hybrids with blowers on them.
Split the turbocharger into a recovery unit, genset, a supercharger and a battery and no more lag.
Weight, size, cost, and loss of efficiency.
There are better things you could do to increase engine performance that are lighter, smaller, and cheaper.
Also of you really really want to defeat turbo lag. The easiest way is to seriously delay ignition timing so the fuel is still burning as it enters the turbine leaving more energy for it to extract and therefore staying spooled up.
edit: Not to say your idea wouldn't work, indeed I'd love to see it. Its just not a practical solution. Not that In ever let practicality stop me.
Edit to the edit: https://dieselnet.com/tech/engine_whr_turbocompound.php
https://www.eere.energy.gov/vehiclesandfuels/pdfs/deer_2004/...
So, ya know, disregard everything above.
There’s been talk for years of just scavenging energy from the exhaust for hybrid drivetrains. To power the peripherals if nothing else.
Part of it is that there’s another reason besides a turbo to have a little extra energy left in the exhaust: thermal catalysis of noxious chemicals in the exhaust flow. So there’s a bit of unburned fuel going to the cat for emissions control and people have wondered if we can take some of it back after the converter. For a while every time there was a breakthrough in solid state heat recovery someone mentioned vehicle exhaust.
A turbocharger isn't a fan. The amount of power it takes to spin is actually incredible. That's why "Electric turbos" were a classic scam until the past decade or so, when they are an extremely weird product that still isn't very good.
Like, producing 1 bar of boost for a 2L engine is somewhere between 30-70 hp! Turbos extract that energy from otherwise wasted, extremely hot exhaust gases, which is what makes them efficient. That's also what made them an improvement over supercharging for the majority of applications, because in a supercharger that energy cost comes direct from your usable power.
What "fixed" turbolag in any engine that isn't an 8L diesel is things like variable geometry, lightweight turbines, better bearings, better engine management, and just smaller turbos for the same boost.
It's also massively impacted by driving behavior. My GTI with a teensy tiny turbo still has a half second or so of lag if you try to go from no throttle to full throttle, like if you are really bad at "launching", but if you know what you are doing you will be holding some revs such that the ECU can slap open the throttle plate and dump fuel in just a few cycles and get full 1 bar of boost by the time your clutch is fully engaged. I have done this accidentally more times than I would like to admit, which tends to spin the tires :/
Formula 1 adopted the exact system you are describing, but it's stupid expensive for minimal benefit and I would bet is used more for energy recovery from waste exhaust gasses than actual lag reduction, since F1 cars should be able to almost never be in a regime that would result in lag, and if you have spare joules, you can just throw them directly at the wheels instead of the turbo. It's called the MGU-H system.
There is already a line of turbos with a motor/generator in the middle but still mechanically coupled https://www.borgwarner.com/technologies/electric-boosting-te...
Using "turbocharged" as a metaphor for something being made faster seems reasonable enough to me. Not all engines have turbochargers, installing one makes it perform better by improving combustion, profit? Of course I'm not a car person so my understanding of an ICE is pretty surface level, but it seems like a decent metaphor.
I'm not sure most people knew what a turbocharger was to begin with.
> Not all engines have turbochargers, installing one makes it perform better by improving combustion, profit?
There are many ways you can make an engine faster. To me the choice of "turbocharger" implies some parallel to the turbochargers actual function, extracting energy from a waste product to process input material at a higher rate.
> The scientists found that birds experiencing the “migration” condition had more mitochondria, and that those mitochondria had a greater capacity to make energy (opens a new tab), compared to those in the “nonmigratory” birds. This suggested that during migration, the birds’ mitochondria are “turbocharged,” Coulson said.
So this isn't too terrible. It's a bit more like overclocking than turbocharging.
A typical ICE turbocharger is a recycler - the exhaust gases are used to spin the turbo which in turn forces air/oxygen into the combustion chamber (cylinder) at a faster rate, which can be tuned alongside fuel intake for increased power.
Of course, this tends to be harder on the engine and must be accounted for in engine design. It's not free, and you don't want every engine to be turbo.
And rather than be good for endurance it's really good for bursts of power.
Rocket engines have turbochargers that run before primary combustion. Just to make things more confusing.
Presumably not off exhaust?
In automobiles, if they are powered by something other than exhaust (e.g. electricity) are called "superchargers."
Ah quick web search, I believe they do run off exhaust using "pre-burners" that burn before the burn.
They make their own exhaust in a little combustion chamber and use it to blast fuel into the primary at ridiculous volumes. SpaceX is unique in that none of the pre burn is wasted. It all ends up back in the bell instead of leaving out the side. The soviets invented it but it never made it to production. I think it flew once and exploded.
I’m not sure I would say the exhaust is wasted just because it doesn’t go into the main combustion chamber. The exhaust of the turbo fuel pump on one Saturn V F-1 engine provides more thrust than an F-16 in afterburner.
The Raptor is the first operational Full Flow Staged Combustion rocket engine. https://en.m.wikipedia.org/wiki/Staged_combustion_cycle#Full...
Combustion cycles that run the turbopump exhaust into the main combustion chamber are called "staged combustion." The Soviets had staged combustion engines putting payloads in orbit in 1960, and the US flew its first in 1981.
SpaceX's advance was going from oxygen rich (where all of the oxidizer and a fraction of the fuel run through the preburner and turbine, as used in the Soviet/Russian engines) or fuel rich (vice versa, used in the Space Shuttle) to full flow (which has both oxygen- and fuel-rich preburners and all of the propellants flow through one turbine or the other).
The rocket folks call them "turbopumps" rather than "turbochargers," and most of them are powered by a separate combustion apparatus (with non-obvious terminology: if, after going through the turbine, the gas will then end up in the main combustion chamber then it's called a preburner, but if the gas will be discharged outside the main combustion chamber then it's called a gas generator).
There is one type that comes closer to a turbocharger's operation: the "tap-off cycle" runs the turbine on gas drawn from the main combustion chamber rather than using a separate combustor. Tap-off cycle engines aren't common but Blue Origin and Firefly are using them.
but thats the semantic drift right?
imagine if i said something like, "after removing all extraneous weight and safety features, my car has been turbocharged."
kinda nonsensical imo, if someone said this i'd just assume they lacked a thesaurus
With the right level of abstraction, we can say that there's only one of four fundamental forces generating the birds' and engine work, electromagnetism, and so maybe can work a relationship about turbos in that way.
Flight relies on gravity. And I wouldn’t want to be a bird experiencing a sudden loss of the Strong or Weak force.
kinda double weird when ATP synthase is said to be a molecular turbine.
we put a turbo in your turbo
Not enough people are old enough to get the more accurate analogy which would be multiple carburetors.
One of my all time favorite molecules. Up there with Actin and DNA itself.
Biology is crazy, man.