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I've learned that mitochondria is thought to have been eaten by a larger cell, resulting the mitochondria to be part of a bigger cell. Well, here's my Q. If you look at how mitochondria works, you find that in order to initiate the TCA cycle, you need to have pyruvate acid.

Then does this mean that when mitochondria was all by itself, there were pyruvate acid around it? I mean, isn't pyruvate acid a complex molecule, therefore, cannot be abundant??? How could this be?

Furthermore, if cell A swallowed a mitochondria, then that cell A should provide mitochondria with NADH and pyruvate acid. How could this be? Did ancient cells produce NADH and pyruvate??

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  • $\begingroup$ Actually it is acetyl CoA that is required for the TCA cycle, not pyruvate. The acetyl CoA can come from other sources, e.g. fatty acids. I agree this doesn't alter the substance of your question. You might do better to wait until you have assimilated more of your course material before posting questions about evolution of metabolism. If you haven't covered photosynthesis yet you can't even start thinking about it. $\endgroup$ – David Aug 15 '16 at 16:26
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    $\begingroup$ Umm sorry... What I mean was, you need acetyl CoA for TCA, but that acetyl CoA is made from pyruvate acid, which $\endgroup$ – Danny Han Aug 15 '16 at 16:31
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    $\begingroup$ Must be entered from outside the mitochondria. In other words, you need pyruvate acid to make mitochondria work. $\endgroup$ – Danny Han Aug 15 '16 at 16:32
  • $\begingroup$ No. As I said, acetyl CoA can come from the breakdown of fatty acids without any involvement of pyruvate. It can come from other intermediates as well. I assume you haven't met these areas of metabolism yet. $\endgroup$ – David Aug 15 '16 at 18:39
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    $\begingroup$ @David Though the OP mentioned pyruvate in specific, there is no real contradiction on it being a substrate. Just that it is not the only substrate. I would rather call Ac-CoA as a reactive intermediate and not a substrate. Organic acids like fatty acids and pyruvic acid (alpha keto acids) are substrates. I see your point but that is not really the central idea of the question. IMO, the idea is where did the ancient mitochondrion obtain its substrates from. An edit would resolve this confusion. $\endgroup$ – WYSIWYG Aug 16 '16 at 8:37
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You are asking a very interesting question.

As you correctly mention, the substrates of mitochondrial metabolism (TCA or Krebs Cycle) are pyruvate and NADH, and, through oxidative reactions, ATP is produced. Indeed, it seems unrealistic that when the "mitochondria" were by themselves there was pyruvate and NADH in the environment. Let's take a step back.

In the 1970s, Dr. Lynn Margulis proposed the extracellular origin of mitochondria. What does this mean? Margulis suggested that, due to the bacteria-like characteristics of mitochondria (e.g. circular DNA), it is plausible that the first mitochondrion was in fact a bacterial cell that had been introduced into another cell by endocytosis. Therefore, we cannot really describe mitochondria as having been "by themselves", since originally they were (most likely) bacteria. (I am emphasizing this because in your statement it seems like perhaps there is some misunderstanding with this point.)

Where were we? Ah, yes, so we have a bacterium (pre-mitochondrion) inside another (host) bacterium. Consider that the combination of one bacterium inside another works and, voilà!, we have symbiosis and, more precisely, endosymbiosis. This means that the two bacteria collaborate to survive, they benefit from interacting with each other (symbiosis) and one of them is inside another (endo-).

But, of course, the combination is not optimal: the two bacteria have common steps in their metabolism and this is a waste of energy. And evolution does not like that. Evolution encourages organisms to minimize their energy expenditure through natural selection: those organisms that manage to make the most out of their energy supplies will survive and thrive. This means that the pairs of endosymbiont bacteria that manage to use less energy to carry out the same actions will be positively selected for.

Indeed, what this possibly lead to was the host bacterium keeping its basic glucose metabolism (glycolysis), and the "inside"-bacterium exclusively keeping its TCA metabolism, effectively becoming a mitochondrion. Hence, the current arrangement of glycolysis in the cytosol and respiration in the mitochondria.

In short, it is important to look at the bigger picture: were there ever really "free" mitochondria? No, according to Margulis' Endosymbiosis Theory there mitochondria-precursors, which were bacteria. Once these bacteria were introduced into the cytoplasm of another cell, their metabolism degenerated and was reduced to the minimum necessary. This is a success story: the mitochondria are evolved bacteria that have managed to survive and thrive, and have made themselves fundamental for survival of many lifeforms, including humans.

I hope this is a useful answer to your question. Feel free to ask for clarifications in case I did not describe something well enough :)

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  • $\begingroup$ As a fun fact, mitochondrial DNA has an extremely low mutation rate, estimated to be one base pair per 7884 years... crazy! Source: genetics.org/content/156/1/297.full $\endgroup$ – rlluc Aug 15 '16 at 9:32
  • $\begingroup$ I have a further question... Bacteria originally had 1 cell membrane, 1 cell wall, and 1 capsule. So then the cell wall and capsule was degenerated while the membrane didn't?? $\endgroup$ – Danny Han Aug 15 '16 at 11:22
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    $\begingroup$ It is thought that a primitive nucleated eukaryote acquired the proteobacterium that gave rise to the mitochondrion — not another bacterium. The later makes little sense and would still have to evolve a nucleus and other features of eukaryotes, lose its cell wall etc. Your answer would be better if you cut 95% out and left the key fact (or hypothesis) that mitochondria were bacteria acquired by primitive eukaryotes that lacked aerobic metabolism. $\endgroup$ – David Aug 15 '16 at 16:15
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    $\begingroup$ @David It is fine to ask someone to remove the 95% of the answer if that was really irrelevant. I don't think that is the case here. $\endgroup$ – WYSIWYG Aug 16 '16 at 8:54
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    $\begingroup$ @rlluc proteobacteria is a class of bacteria and extant α-proteobacteria and mitochondria fall under the same phylogenetic group (clade). Therefore it is believed that the ancient mitochondrial ancestor would have been a bacteria of the α-proteobacteria group. The details of how this happened are still unknown. $\endgroup$ – WYSIWYG Aug 16 '16 at 9:26

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