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)
Aurornis · 4h ago
> 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.
smj-edison · 13m ago
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 :)
ajb · 46m ago
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".
loa_in_ · 3h ago
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.
Can you elaborate, what is this based on?
treyd · 1h ago
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.
CooCooCaCha · 3h ago
What would be the root cause then?
kridsdale1 · 2h ago
More grant funding needed to answer.
CooCooCaCha · 3h ago
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.
HarHarVeryFunny · 8m ago
Sounds horrible! I'm glad you recovered!
parpfish · 5h ago
mitochondria is the powerhouse of the fatigue research
koeng · 15m ago
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.
jonplackett · 3h ago
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)
xg15 · 2h ago
Also if this is something that is specific to the birds' mitochondria or could be triggered in mitochondria of any species.
kridsdale1 · 2h ago
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.
mulmen · 2h ago
> 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?
sigmaisaletter · 1h ago
"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."
i.e. mtDNA changes a lot less than our "normal" cell nucleus nDNA
kridsdale1 · 2h ago
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.
parpfish · 5h ago
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.
gherkinnn · 4h ago
You're behind the times, turbo has drifted (heh) far in to meaning 'fast' of sorts:
Don’t forget the turbo button, which is almost as old as turbo pascal.
jonplackett · 3h ago
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.
hinkley · 3h ago
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.
acdha · 3h ago
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.
hinkley · 3h ago
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.
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)!
hinkley · 4h ago
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.
MadnessASAP · 4h ago
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.
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.
xeonmc · 1h ago
So like the MGU-H? Or the new always-stoichiometric 911?
jchw · 5h ago
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.
zardo · 4h ago
> 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.
neogodless · 5h ago
> 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.
hinkley · 4h ago
Rocket engines have turbochargers that run before primary combustion. Just to make things more confusing.
neogodless · 4h ago
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.
hinkley · 3h ago
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.
mulmen · 2h ago
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.
“Blown” is often more accurate but it sounds dirty.
nh23423fefe · 5h ago
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
nh23423fefe · 5h ago
kinda double weird when ATP synthase is said to be a molecular turbine.
we put a turbo in your turbo
kridsdale1 · 2h ago
One of my all time favorite molecules. Up there with Actin and DNA itself.
Biology is crazy, man.
hinkley · 4h ago
Not enough people are old enough to get the more accurate analogy which would be multiple carburetors.
762236 · 5h ago
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.
kridsdale1 · 2h ago
Flight relies on gravity. And I wouldn’t want to be a bird experiencing a sudden loss of the Strong or Weak force.
CGMthrowaway · 5h ago
In fairness, they put "turbocharged" in quotes.
m3kw9 · 5h ago
Was gonna say, do they know how turbos work?
aurizon · 5h ago
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/
koeng · 17m ago
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
reubenswartz · 1h ago
There are ~100,000 mitochondria in a human egg cell-- I think that's a pretty tall order.
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.
aurizon · 24m ago
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?
ChrisArchitect · 3h ago
Related:
Mitochondria Are More Than Powerhouses–They're the Motherboard of the Cell
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.
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 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.
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.
(FYI I’m not a biologist and have no idea what I’m talking about)
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.
But how much has our mitochondria differed in that time?
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
- 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":
https://news.ycombinator.com/item?id=42865194
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.
Too late.
https://www.porsche.com/usa/models/taycan/taycan-models/tayc...
Split the turbocharger into a recovery unit, genset, a supercharger and a battery and no more lag.
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.
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.
I'm not sure most people knew what a turbocharger was to begin with.
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.
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.
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.
The Raptor is the first operational Full Flow Staged Combustion rocket engine. https://en.m.wikipedia.org/wiki/Staged_combustion_cycle#Full...
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
we put a turbo in your turbo
Biology is crazy, man.
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
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.
Mitochondria Are More Than Powerhouses–They're the Motherboard of the Cell
https://news.ycombinator.com/item?id=44052909