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As we were told during high school biology: cardiovascular muscle contains vast amounts of mitochondria as compared to other muscle types. Mitochondria are good

As we were told during high school biology: cardiovascular muscle contains vast amounts of mitochondria as compared to other muscle types. Mitochondria are good. Therefore, more and stronger mitochondria = more efficient working muscle tissue. One of my favorite professors holds a PhD in kinesiology (exercise physiology concentration) and wrote his dissertation on the mitochondria. As he stated many times in class: if you want to have a superhuman composition, acquire more mitochondria. he was always willing to bet his kids entire college tuition funds if you could show him a pill that would produce more mitochondria.

chrisco255 7y ago
I wonder what the trade-offs would be if you could amplify mitochondria in skeletal muscle?
- bamboozled 7y ago
  I'm pretty sure this is what happens if you're a weight lifter?
  - usrusr 7y ago
    Weight lifting isn't an endurance sport. If you want mitochondria obsession, look for anything long distance.
    - labawi 7y ago
      Non-repetitive weight lifting wouldn't be a good example, but neither is anything in 10s of km. Mitochondria produce ATP as energy. You can't store much¹ ATP, therefore mitochondria must be capable of producing ATP at your near peak output (say 10s average). I'd look at anything with high >10s peak power (probably a bonus if it's aerobic). Many bodybuilding exercises would qualify. ¹ Lactic acid is a byproduct of ATP production, therefore ATP supplies surely last less, than what it takes to start producing lots of lactic acid.
- DoreenMichele 7y ago
  As a guess: You would be unable to rest without utter exhaustion, and possibly even not then. You might need to keep flexing your muscles constantly.
  - smabie 7y ago
    Why would that be?
    - DoreenMichele 7y ago
      I'm basing it off of this comment: https://news.ycombinator.com/item?id=22643333 https://news.ycombinator.com/item?id=22643333 And this follow-up comment sort of agrees with my inference -- at least the first part of my inference: https://news.ycombinator.com/item?id=22644577 https://news.ycombinator.com/item?id=22644577 Edit: I will add that I am also, no doubt, basing it off of background knowledge about cell function. For example, mitochondria change and develop greater capacity to process X if you consume a lot of it, which is part of the addiction process and part of why withdrawal is a thing. If you consume a lot of, say, alcohol, you need to ramp down gradually so that the body can make changes at the cellular level to adjust to the lesser amount of alcohol and this is part of why cold turkey is so very hard and it is generally recommended that you taper off. I used to ask smart people with PhDs and the like a lot of questions about cell function and read what I could get my hands on that could be followed by a lay person because I have a genetic disorder that impacts cell function.
  - hobofan 7y ago
    There are other cell types that have a strongly increased amount of mitochondria like brown adipose tissue. They also don't have a "need" to perform some work constantly. As with any cell function how much work mitochondria perform is highly regulated. Just because you have a lot of them doesn't mean you can't turn their function down.
    - DoreenMichele 7y ago
      Nadia Commenci was recruited as a gymnast at age five because she was too active and breaking the furniture at home. She made the first ever perfect 10 score in the Olympics. They didn't have a way to display it. It got displayed as 1.00 because they only had three spaces on the sign. Her best friend became a professional ballerina. I have heard that Chuck Norris does two workouts a day and if he skips one, he makes everyone around him crazy. If he does two per day, he's calm, cool and collected and fine to be around. If he doesn't, welp, he can't sit still and he can't control his mouth and he bounces off the walls and everyone can't stand him. I also talked about the addiction process and mitochondrial function in a different comment.
- ChuckMcM 7y ago
  You become more chimp like.
- gameswithgo 7y ago
  you would need more red blood cells to feed them, and at sone point that puts you at risk for a heart attack because your blood is too thick
  - nradov 7y ago
    That's not a realistic risk unless you have some rare medical condition or are doping with a PED like EPO.
- PeterisP 7y ago
  The cells would consume more energy, so you'd need more food, so in conditions of food scarcity (i.e. 99% of our [pre]history) you would be at a severe disadvantage as your tribe would starve to death in conditions when more efficient homo sapiens would still survive.
  - EamonnMR 7y ago
    Also require more oxygen and produce more heat.
justinator 7y ago
Mitochondria are the powerhouse of the cell.
- charles_f 7y ago
  Mitochondria are the powerhouse of the cell x2 in the heart
- rootsudo 7y ago
  I love this meme.
  - stjohnswarts 7y ago
    It's not a meme, it's an analogy.
    - falcor84 7y ago
      Well, it definitely is a meme as defined by Dawkins[0]. In general, I would say that analogies and metaphors like this one have a huge impact on normal science, and are one of the main things that change during a paradigm shift. I recall a great example in how 150 years ago people thought of the body's physiology as analogous to a steam engine with downstream effects due to pressure building up, contrasted to how in today's computer age, we tend to think of physiology in terms of signal processing. [0] https://en.wikipedia.org/wiki/Memetics https://en.wikipedia.org/wiki/Memetics
      - lioeters 7y ago
        I agree, the imagery that we use in metaphor (in speech, visually, or in conception) influences how we think about things - and a popular analogy like that about the mitochondria is certainly a meme, a "cultural information transfer". As you pointed out, a fairly recent meme is "the brain is the computer of the body", and maybe "the Internet is the brain of humanity".
hyperdunc 7y ago
Then I guess the obvious question a non-physiologist would ask is, why don't all our muscles already have vast amounts of mitochondria? If it's that beneficial with no major downsides then surely evolution would have stumbled on that configuration already?
- ivalm 7y ago
  Mitochondria do produce a lot of free radicals. Probably energy expensive to maintain cells like that.
  - rolph 7y ago
    not only energy expensive but free radicals do genetic damage, and a this requires the second budget for a set of enzymes to counteract the damages and scrub out FR's
    - lumost 7y ago
      Why isn't Heart Cancer more common if it's producing so many free radicals? Are there other mechanisms blocking genetic damage?
      - dodobirdlord 7y ago
        Muscle cells don't replicate past early childhood development, they just get bigger and add more nuclei. So muscle cancers are extremely rare compared to cancers of other tissues.
        rolph 7y ago
        each nucleus contains a full genomic content. muscles are more of a "myosynsynctium" than a group of cells. there are cohorts of cells that are more prone to becoming cancer due to thier developmental origins and the complement of developmental mechanisms that can be reactivated. things such as cell adhesion, and cell migration through tissue dermal cells are good at this as they do these things over the course of development. muscles are built where they will live so these features are inhibited somewhat more completely and harder to "switch on or off"
ramraj07 7y ago
He would have lost his sons college thition then. Mitochondrial _inhibition_ is actually more correlated with longevity than the other way around. If more mitochondria meant more efficient working muscle tissue, then that's what we would have evolved, there's always a compromise. Are you sure you can keep the same power output for a given mass and volume of muscle if you keep increasing mitochondrial numbers? Even the reddit answer clearly says that the heart muscle is rate limited by oxygenation (they have more mitochondria but are also highly vascularized to power the mitochondria). More mitochondria===more power doesn't mean it's better for us, physiology is rarely that simple.
- catalogia 7y ago
  > Mitochondrial _inhibition_ is actually more correlated with longevity than the other way around. Longevity is overrated. The light that burns twice as bright lives half as long. I'd rather be a superhuman for 40 years than feeble for 120 years.
  - TheSpiceIsLife 7y ago
    As I understand it, longevity in the life-extension sense is generally taken to mean years of good health. Edit: fixed a word.
  - goatinaboat 7y ago
    I'd rather be a superhuman for 40 years than feeble for 120 years. But that’s not a choice you can actually make, it’s out of your control. What if you could choose by taking a pill?
  - rubber_duck 7y ago
    Steroids let you control this trade-off
  - ci5er 7y ago
    Maybe yes, maybe no. But evolution didn't decide on the structure and behavior of our throw-away-cup bodies in order to make our puny minds sitting on top our puny brains happy. For better or for worse, in humans (we are not turtles, for example, they have their own success strategy), AVERAGE 2nd generation reproductive success is the measure of our existence. The collection of strategies to maximize that are different for human men and human women. But aligned. On average. 2nd-generation reproductive success is our "purpose" in a universe made mostly out of hydrogen. Nothing more - nothing less.
jldugger 7y ago
> he was always willing to bet his kids entire college tuition funds if you could show him a pill that would produce more mitochondria. Did he mention whether faculty get free family tuition or not?
- ikeyany 7y ago
  His children will be made to forego college in order to trailblaze the up and coming trade of mitochondria hunting.
  - im3w1l 7y ago
    I read it as him claiming that investing in it would be a sure bet.
hkmurakami 7y ago
This just reminded me of the game Parasite Eve.
heartisnt001 7y ago
I am going to hijack this top comment. > If the heart is a muscle, why doesn't it get tired? Because it's illogical to assume muscles fatigue. They physically don't get to the point where they can no longer operate -- under normal everyday use and exercise. What does happen, that may seem like fatigue, is a gradual shifting of fuel sources by muscle cells depending on exertion levels. Suffice to say, it goes like this: - First: Creatine Phosphate is the first energy source in your muscles, the most powerful one, and the least plentiful. It's the first to go during exercise and is partly why you focus on 1-5 reps for strength-focused lifting (that's roughly how long it takes to get used up) - Second: Glycogen in your muscles and liver. This is fairly plentiful, fairly powerful, and rapidly mobilizeable. After your creatine phosphate stores are emptied, glycogen takes over. This is still a very powerful fuel source, but its metabolism creates a negative feedback loop on itself. You can only sustain moderate exertion (see: sprinting or 8-15 reps moderate weight) for around 60-90 seconds, before glycogen is no longer easily accessible (note: accessible, not depleted. It's almost impossible to deplete in a single workout) - Finally: Fat. Once you've exhausted glycogen, your body turns to fatty acid oxidation. This is the least powerful but most plentiful. In normal exercise you use a mix of fat and glycogen depending on how hard you exert yourself. Harder: more glycogen. Easier: more fat. If you want to know how it feels like to run on only fat: do a marathon -- then hit the wall. What you experience is literally the complete depletion of glycogen, and a transition into "low-power" mode as your body starts running on the only fuel source it has left: fat. You have months of this fuel source on your body, you won't run out. You can keep walking for days without having eaten anything or slept, but you won't be able to run at any pace that resembles a jog. I know, because I have. What's the point of all this? It's to illustrate that muscle "exhaustion" is a misnomer. Muscle exhaustion is, in reality, a depletion of power-generating fuels leading to a state of minimal exertion. Coincidentally, that's the mode the heart operates in 24/7. Coincidentally, the heart has an asinine amount of mitochondria to fuel non-stop fatty acid oxidation. The heart doesn't fatigue because it's not physically possible. It doesn't need creatine phosphate or glycogen (very very little) to pump blood. It's not a strenuous task. An aside: if you had as much mitochondria in all your cells, as you do in your heart's, you would waste away.
- raidicy 7y ago
  Some anecdata but, I suffered from very bad muscle injuries from one summer in 2014. I skateboarded hard for two days in a row. Ran 3-ish miles on both days. Two days later I was exhausted but took two ibuprofen and I went to a beach with friends anyway. Where I skated hard at a park for a few hours, then swam, then ran. A day or so later, after not getting the best sleep, on an hour drive home, I pull both quads. The day after I had to call out for a week. I was exhausted and my obliques, core, quads, and arms were beyond sore. I laid around for most of the week. Your muscles may not get "exhausted" but it seems like there must be some breakdown in the cells that outpace recovery at some point.
loeg 7y ago
> he was always willing to bet his kids entire college tuition funds if you could show him a pill that would produce more mitochondria. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737409/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737409/ aka https://en.wikipedia.org/wiki/SR9009 https://en.wikipedia.org/wiki/SR9009
- lioeters 7y ago
  Good stuff! > Activation of Rev-ErbA-α by SR9009 in mice increases exercise capacity by increasing mitochondria counts in skeletal muscle. > Some companies are selling SR9009 online for human use as a 'research chemical'. > "The drug [alters] the circadian rhythm (in mice) and we would need to assume in humans – and we don't know if it is beneficial or detrimental at this point." --- It has "several issues that make it unsuitable for human use". > Firstly, it has no oral bioavailability. I know the company selling this is indicating taking it orally is ok – but it doesn't even get into the blood. > SR9009 has some functional groups that are known to have potential toxicology liabilities and it would never be developed as a drug. > So bottom line – I would never recommend using this compound at this point. That being said – we are still working on improved compounds with one of the potential uses being sarcopenia – loss of muscle and strength due to aging.
peter_retief 7y ago
Aren't mitochondria captive cells from early evolutionary times? I googled and from nature.com "Mitochondria and chloroplasts likely evolved from engulfed prokaryotes that once lived as independent organisms. At some point, a eukaryotic cell engulfed an aerobic prokaryote, which then formed an endosymbiotic relationship with the host eukaryote, gradually developing into a mitochondrion."

chrisco255 7y ago

I wonder what the trade-offs would be if you could amplify mitochondria in skeletal muscle?

bamboozled 7y ago
I'm pretty sure this is what happens if you're a weight lifter?
- usrusr 7y ago
  Weight lifting isn't an endurance sport. If you want mitochondria obsession, look for anything long distance.
  - labawi 7y ago
    Non-repetitive weight lifting wouldn't be a good example, but neither is anything in 10s of km. Mitochondria produce ATP as energy. You can't store much¹ ATP, therefore mitochondria must be capable of producing ATP at your near peak output (say 10s average). I'd look at anything with high >10s peak power (probably a bonus if it's aerobic). Many bodybuilding exercises would qualify. ¹ Lactic acid is a byproduct of ATP production, therefore ATP supplies surely last less, than what it takes to start producing lots of lactic acid.
DoreenMichele 7y ago
As a guess: You would be unable to rest without utter exhaustion, and possibly even not then. You might need to keep flexing your muscles constantly.
- smabie 7y ago
  Why would that be?
  - DoreenMichele 7y ago
    I'm basing it off of this comment: https://news.ycombinator.com/item?id=22643333 https://news.ycombinator.com/item?id=22643333 And this follow-up comment sort of agrees with my inference -- at least the first part of my inference: https://news.ycombinator.com/item?id=22644577 https://news.ycombinator.com/item?id=22644577 Edit: I will add that I am also, no doubt, basing it off of background knowledge about cell function. For example, mitochondria change and develop greater capacity to process X if you consume a lot of it, which is part of the addiction process and part of why withdrawal is a thing. If you consume a lot of, say, alcohol, you need to ramp down gradually so that the body can make changes at the cellular level to adjust to the lesser amount of alcohol and this is part of why cold turkey is so very hard and it is generally recommended that you taper off. I used to ask smart people with PhDs and the like a lot of questions about cell function and read what I could get my hands on that could be followed by a lay person because I have a genetic disorder that impacts cell function.
- hobofan 7y ago
  There are other cell types that have a strongly increased amount of mitochondria like brown adipose tissue. They also don't have a "need" to perform some work constantly. As with any cell function how much work mitochondria perform is highly regulated. Just because you have a lot of them doesn't mean you can't turn their function down.
  - DoreenMichele 7y ago
    Nadia Commenci was recruited as a gymnast at age five because she was too active and breaking the furniture at home. She made the first ever perfect 10 score in the Olympics. They didn't have a way to display it. It got displayed as 1.00 because they only had three spaces on the sign. Her best friend became a professional ballerina. I have heard that Chuck Norris does two workouts a day and if he skips one, he makes everyone around him crazy. If he does two per day, he's calm, cool and collected and fine to be around. If he doesn't, welp, he can't sit still and he can't control his mouth and he bounces off the walls and everyone can't stand him. I also talked about the addiction process and mitochondrial function in a different comment.
ChuckMcM 7y ago
You become more chimp like.
gameswithgo 7y ago
you would need more red blood cells to feed them, and at sone point that puts you at risk for a heart attack because your blood is too thick
- nradov 7y ago
  That's not a realistic risk unless you have some rare medical condition or are doping with a PED like EPO.
PeterisP 7y ago
The cells would consume more energy, so you'd need more food, so in conditions of food scarcity (i.e. 99% of our [pre]history) you would be at a severe disadvantage as your tribe would starve to death in conditions when more efficient homo sapiens would still survive.
- EamonnMR 7y ago
  Also require more oxygen and produce more heat.

justinator 7y ago

Mitochondria are the powerhouse of the cell.

charles_f 7y ago
Mitochondria are the powerhouse of the cell x2 in the heart
rootsudo 7y ago
I love this meme.
- stjohnswarts 7y ago
  It's not a meme, it's an analogy.
  - falcor84 7y ago
    Well, it definitely is a meme as defined by Dawkins[0]. In general, I would say that analogies and metaphors like this one have a huge impact on normal science, and are one of the main things that change during a paradigm shift. I recall a great example in how 150 years ago people thought of the body's physiology as analogous to a steam engine with downstream effects due to pressure building up, contrasted to how in today's computer age, we tend to think of physiology in terms of signal processing. [0] https://en.wikipedia.org/wiki/Memetics https://en.wikipedia.org/wiki/Memetics
    - lioeters 7y ago
      I agree, the imagery that we use in metaphor (in speech, visually, or in conception) influences how we think about things - and a popular analogy like that about the mitochondria is certainly a meme, a "cultural information transfer". As you pointed out, a fairly recent meme is "the brain is the computer of the body", and maybe "the Internet is the brain of humanity".

hyperdunc 7y ago

Then I guess the obvious question a non-physiologist would ask is, why don't all our muscles already have vast amounts of mitochondria? If it's that beneficial with no major downsides then surely evolution would have stumbled on that configuration already?

ivalm 7y ago
Mitochondria do produce a lot of free radicals. Probably energy expensive to maintain cells like that.
- rolph 7y ago
  not only energy expensive but free radicals do genetic damage, and a this requires the second budget for a set of enzymes to counteract the damages and scrub out FR's
  - lumost 7y ago
    Why isn't Heart Cancer more common if it's producing so many free radicals? Are there other mechanisms blocking genetic damage?
    - dodobirdlord 7y ago
      Muscle cells don't replicate past early childhood development, they just get bigger and add more nuclei. So muscle cancers are extremely rare compared to cancers of other tissues.
      - rolph 7y ago
        each nucleus contains a full genomic content. muscles are more of a "myosynsynctium" than a group of cells. there are cohorts of cells that are more prone to becoming cancer due to thier developmental origins and the complement of developmental mechanisms that can be reactivated. things such as cell adhesion, and cell migration through tissue dermal cells are good at this as they do these things over the course of development. muscles are built where they will live so these features are inhibited somewhat more completely and harder to "switch on or off"

ramraj07 7y ago

He would have lost his sons college thition then. Mitochondrial _inhibition_ is actually more correlated with longevity than the other way around. If more mitochondria meant more efficient working muscle tissue, then that's what we would have evolved, there's always a compromise. Are you sure you can keep the same power output for a given mass and volume of muscle if you keep increasing mitochondrial numbers? Even the reddit answer clearly says that the heart muscle is rate limited by oxygenation (they have more mitochondria but are also highly vascularized to power the mitochondria). More mitochondria===more power doesn't mean it's better for us, physiology is rarely that simple.

catalogia 7y ago
> Mitochondrial _inhibition_ is actually more correlated with longevity than the other way around. Longevity is overrated. The light that burns twice as bright lives half as long. I'd rather be a superhuman for 40 years than feeble for 120 years.
- TheSpiceIsLife 7y ago
  As I understand it, longevity in the life-extension sense is generally taken to mean years of good health. Edit: fixed a word.
- goatinaboat 7y ago
  I'd rather be a superhuman for 40 years than feeble for 120 years. But that’s not a choice you can actually make, it’s out of your control. What if you could choose by taking a pill?
- rubber_duck 7y ago
  Steroids let you control this trade-off
- ci5er 7y ago
  Maybe yes, maybe no. But evolution didn't decide on the structure and behavior of our throw-away-cup bodies in order to make our puny minds sitting on top our puny brains happy. For better or for worse, in humans (we are not turtles, for example, they have their own success strategy), AVERAGE 2nd generation reproductive success is the measure of our existence. The collection of strategies to maximize that are different for human men and human women. But aligned. On average. 2nd-generation reproductive success is our "purpose" in a universe made mostly out of hydrogen. Nothing more - nothing less.

jldugger 7y ago

> he was always willing to bet his kids entire college tuition funds if you could show him a pill that would produce more mitochondria. Did he mention whether faculty get free family tuition or not?

ikeyany 7y ago
His children will be made to forego college in order to trailblaze the up and coming trade of mitochondria hunting.
- im3w1l 7y ago
  I read it as him claiming that investing in it would be a sure bet.

hkmurakami 7y ago

This just reminded me of the game Parasite Eve.

heartisnt001 7y ago

I am going to hijack this top comment. > If the heart is a muscle, why doesn't it get tired? Because it's illogical to assume muscles fatigue. They physically don't get to the point where they can no longer operate -- under normal everyday use and exercise. What does happen, that may seem like fatigue, is a gradual shifting of fuel sources by muscle cells depending on exertion levels. Suffice to say, it goes like this: - First: Creatine Phosphate is the first energy source in your muscles, the most powerful one, and the least plentiful. It's the first to go during exercise and is partly why you focus on 1-5 reps for strength-focused lifting (that's roughly how long it takes to get used up) - Second: Glycogen in your muscles and liver. This is fairly plentiful, fairly powerful, and rapidly mobilizeable. After your creatine phosphate stores are emptied, glycogen takes over. This is still a very powerful fuel source, but its metabolism creates a negative feedback loop on itself. You can only sustain moderate exertion (see: sprinting or 8-15 reps moderate weight) for around 60-90 seconds, before glycogen is no longer easily accessible (note: accessible, not depleted. It's almost impossible to deplete in a single workout) - Finally: Fat. Once you've exhausted glycogen, your body turns to fatty acid oxidation. This is the least powerful but most plentiful. In normal exercise you use a mix of fat and glycogen depending on how hard you exert yourself. Harder: more glycogen. Easier: more fat. If you want to know how it feels like to run on only fat: do a marathon -- then hit the wall. What you experience is literally the complete depletion of glycogen, and a transition into "low-power" mode as your body starts running on the only fuel source it has left: fat. You have months of this fuel source on your body, you won't run out. You can keep walking for days without having eaten anything or slept, but you won't be able to run at any pace that resembles a jog. I know, because I have. What's the point of all this? It's to illustrate that muscle "exhaustion" is a misnomer. Muscle exhaustion is, in reality, a depletion of power-generating fuels leading to a state of minimal exertion. Coincidentally, that's the mode the heart operates in 24/7. Coincidentally, the heart has an asinine amount of mitochondria to fuel non-stop fatty acid oxidation. The heart doesn't fatigue because it's not physically possible. It doesn't need creatine phosphate or glycogen (very very little) to pump blood. It's not a strenuous task. An aside: if you had as much mitochondria in all your cells, as you do in your heart's, you would waste away.

raidicy 7y ago
Some anecdata but, I suffered from very bad muscle injuries from one summer in 2014. I skateboarded hard for two days in a row. Ran 3-ish miles on both days. Two days later I was exhausted but took two ibuprofen and I went to a beach with friends anyway. Where I skated hard at a park for a few hours, then swam, then ran. A day or so later, after not getting the best sleep, on an hour drive home, I pull both quads. The day after I had to call out for a week. I was exhausted and my obliques, core, quads, and arms were beyond sore. I laid around for most of the week. Your muscles may not get "exhausted" but it seems like there must be some breakdown in the cells that outpace recovery at some point.

loeg 7y ago

> he was always willing to bet his kids entire college tuition funds if you could show him a pill that would produce more mitochondria. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737409/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737409/ aka https://en.wikipedia.org/wiki/SR9009 https://en.wikipedia.org/wiki/SR9009

lioeters 7y ago
Good stuff! > Activation of Rev-ErbA-α by SR9009 in mice increases exercise capacity by increasing mitochondria counts in skeletal muscle. > Some companies are selling SR9009 online for human use as a 'research chemical'. > "The drug [alters] the circadian rhythm (in mice) and we would need to assume in humans – and we don't know if it is beneficial or detrimental at this point." --- It has "several issues that make it unsuitable for human use". > Firstly, it has no oral bioavailability. I know the company selling this is indicating taking it orally is ok – but it doesn't even get into the blood. > SR9009 has some functional groups that are known to have potential toxicology liabilities and it would never be developed as a drug. > So bottom line – I would never recommend using this compound at this point. That being said – we are still working on improved compounds with one of the potential uses being sarcopenia – loss of muscle and strength due to aging.

peter_retief 7y ago

Aren't mitochondria captive cells from early evolutionary times? I googled and from nature.com "Mitochondria and chloroplasts likely evolved from engulfed prokaryotes that once lived as independent organisms. At some point, a eukaryotic cell engulfed an aerobic prokaryote, which then formed an endosymbiotic relationship with the host eukaryote, gradually developing into a mitochondrion."