What keeps mitochondria from multiplying out of control and killing the cell?

According to endosymbiotic theory, mitochondria were once free-living bacteria that got ingested but not metabolized by the host cell. What prevents mitochondria from replicating out of control and overpowering the host cell? The question was inspired by this brainstorming session about engineered endosymbiosis.

  • $\begingroup$ Could you please add some more details or show some sign of research on your own? E.g. any citations on mitochondrial replication? $\endgroup$ – Maximilian Press Oct 29 '20 at 19:17
  • $\begingroup$ It seems like a pretty straightforward and self-sufficient question. What would be the purpose of adding such a paragraph? I'm not against it, I'm just trying to understand the rationale $\endgroup$ – Retardi Grade Oct 30 '20 at 20:59
  • $\begingroup$ well, as your accepted answer begins, "I'm guessing at the motivation of your question..." I think jamesqf does a good job of rephrasing the question into something that's a lot easier to answer. $\endgroup$ – Maximilian Press Oct 30 '20 at 21:35
  • $\begingroup$ err. i mean acvill. those are more answerable questions. Additionally, you should have provided your brainstorming link in the first place if that was where you were coming from. $\endgroup$ – Maximilian Press Oct 30 '20 at 21:50
  • $\begingroup$ I hope this fixes it $\endgroup$ – Retardi Grade Nov 1 '20 at 8:22

I'm guessing at the motivation for your question -- In the evolutionary history of eukaryotic cells, mitochondria were once free-living bacteria. What prevents them from acting as intracellular pathogens and replicating out-of-control?

Yes, by endosymbiotic theory 1, mitochondria were once free-living prokaryotic organisms. This is evident because they have their own DNA, undergo replication by fission, and have characteristics similar to proteobacteria.

However, some of the genes required for mitochondrial replication have been moved to the nuclear genome. This means that, while mitochondrial replication is not necessarily tied to cell replication, factors encoded in the nucleus are necessary for mitochondrial replication.2

  1. https://en.wikipedia.org/wiki/Symbiogenesis
  2. Ali, et al. Nuclear genetic regulation of the human mitochondrial transcriptome. eLife 2019;8:e41927.
  • $\begingroup$ That's all I needed to hear:) The question was actually motivated by this brainstorming session about engineered endosymbiosis brainstorming.com/r/s164 $\endgroup$ – Retardi Grade Oct 14 '20 at 15:19
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    $\begingroup$ I think we might have to go back further than the present situation. A bacterium couldn't become a successful endosymbiont if it multiplied out of control and killed its host, and it would seem that this non-lethal behavior must have existed long before evolution moved the genes around. $\endgroup$ – jamesqf Oct 14 '20 at 16:06
  • $\begingroup$ Good point. I will set the question as not answered to see if we can come up with something that accounts for this. Dirigible did solve the question I had in mind, but now that you mention this plot twist, I would love to know:) $\endgroup$ – Retardi Grade Oct 14 '20 at 16:38
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    $\begingroup$ jamesqf's point is a good one. However, the original question was "What keeps mitochondria from multiplying out of control and killing the cell?", not "What factors contributed to the intracellular symbiosis that led to mitochondria?" Post a new question (with preliminary research / thoughts) if you want a new answer. It's poor etiquette to post a question, accept an answer, add more questions, and remove your accept. $\endgroup$ – acvill Oct 14 '20 at 20:17
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    $\begingroup$ @RetardiGrade I think you should look up retrograde signalling between the Nucleus and mitochondria if you would like to know the molecular mechanism regulating mitochondrial numbers. $\endgroup$ – Roni Saiba Nov 1 '20 at 17:52

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