Imagine a negotiation bid that took place billions of years ago. One
bacterial system tells another, "Hey, know what would be really cool? If I
got into you and helped light up your place, get you some energy and in turn,
you protect me from annihilation"
The second bacterial guy scratches its
imaginary head and says, "Well, okay. But you gotta figure out a way to shut
off that energy-making when I don’t need it. I can’t stand the racket you make”
“Deal”
That’s the story of how we got mitochondria within nearly every cell we
possess. And in accordance with the treaty of yore, they reside within the
cells, do all the dirty work and in return, get access to nutrients, protection
from other microbes and harmful chemicals, companionship and love.
And because they weren't total pushovers in that above-mentioned treaty, they got to keep their own DNA. The DNA they have right now is exactly what they need for their primary purpose of energy production. Now, being savvy packers, it might be that they shed some genetic baggage that we don't know much about. But the end result is that we actually carry two pockets of DNA within each of our cells: the check-in baggage that contains the bulk of our DNA stored neatly within the nucleus and our little mitochondrial carry-ons.
Where there is DNA, there is genetics. Of course. Mitochondrial genetics is very different from the nuclear genetics that we know and love so well (ha!). For one, ALL the mitochondrial DNA you have within you comes directly from your mom, and nobody else. So you can sequence every person's mitochondrial DNA and trace back your maternal ancestors. And indeed, when people did that, they figured out the entire migratory routes of womankind (yes, you tagged along too, silly males!)
Here's a nice pic showing human migration from the Professor Taboo blog:
Mitochondrial DNA can get mutated, just like the DNA in the nucleus. But unlike the nuclear DNA, mtDNA has no protein complexes, called nucleosomes, enveloping it making it more susceptible to mutations. But on the plus side, there are many mitochondria within each cell. So even if one mitochondrion has mutated DNA, the cell might still function just fine if the rest of the mitos within it are normal. It is all a matter of dosage.
Problems arise when many or most mitochondria end up carrying mutated DNA.
A really cool theory goes like this: Mitochondria accumulate mutations over time. Initially it may be a few mitos that carry mutated DNA, then a few more, and a few more. Even if new mitos are being formed, they arise from mitos that are carrying mutations. So, the new cells in your body are less efficient and more prone to mistakes. Ultimately, new cells may not be produced at all, because there are just too many mutations in the mtDNA. This is what leads to aging and the development of degenerative diseases.
What an interesting concept, no? It forces you to think about your body like a car or a machine. Since mitochondria produce energy, mutations in their DNA can affect the amount of energy each cell produces. As mtDNA mutations accumulate, the efficiency of conversion of food to energy drops off, cell by cell and then organ by organ. It's like an old car that cannot run anymore. It's basic thermodynamics at work: a body needs an energy infusion to keep it running. No more energy, no more running.
As more and more researchers leap on the mito-bandwagon, it is becoming clear that mitochondrial energetics can, at least partially, explain a number of complex diseases or symptoms, including cancer, diabetes, cardiovascular disease and obesity-associated diseases.
Let me conclude this post with another very interesting theory, which goes back to the dosage effect mentioned earlier: different dosages of the same mtDNA mutation can lead to different effects. A small dosage (only a few mutated mitochondria) might lead to a disease like retinitis pigmentosa, leading to blindness in middle-age, a larger dose might lead to blindness at an earlier age, a still larger dose might lead to early death, while at very high dosage, the mutation might cause stillbirths or miscarriages.
What fascinating stuff! Suddenly, a whole new way by which we think about diseases, their pathology and development has opened up. Very different diseases may actually all arise from the same cause!
How does mtDNA get mutated upon different environmental insults like smoking or drinking polluted water? How do mitochondria compensate for their mutated and less efficient brethren? How do nuclear DNA and mtDNA interact, if at all? And finally, what can we do about mtDNA mutations pharmacologically?
Hopefully we find the answers to these and more questions.
Mitochondrial DNA can get mutated, just like the DNA in the nucleus. But unlike the nuclear DNA, mtDNA has no protein complexes, called nucleosomes, enveloping it making it more susceptible to mutations. But on the plus side, there are many mitochondria within each cell. So even if one mitochondrion has mutated DNA, the cell might still function just fine if the rest of the mitos within it are normal. It is all a matter of dosage.
Problems arise when many or most mitochondria end up carrying mutated DNA.
A really cool theory goes like this: Mitochondria accumulate mutations over time. Initially it may be a few mitos that carry mutated DNA, then a few more, and a few more. Even if new mitos are being formed, they arise from mitos that are carrying mutations. So, the new cells in your body are less efficient and more prone to mistakes. Ultimately, new cells may not be produced at all, because there are just too many mutations in the mtDNA. This is what leads to aging and the development of degenerative diseases.
What an interesting concept, no? It forces you to think about your body like a car or a machine. Since mitochondria produce energy, mutations in their DNA can affect the amount of energy each cell produces. As mtDNA mutations accumulate, the efficiency of conversion of food to energy drops off, cell by cell and then organ by organ. It's like an old car that cannot run anymore. It's basic thermodynamics at work: a body needs an energy infusion to keep it running. No more energy, no more running.
As more and more researchers leap on the mito-bandwagon, it is becoming clear that mitochondrial energetics can, at least partially, explain a number of complex diseases or symptoms, including cancer, diabetes, cardiovascular disease and obesity-associated diseases.
Let me conclude this post with another very interesting theory, which goes back to the dosage effect mentioned earlier: different dosages of the same mtDNA mutation can lead to different effects. A small dosage (only a few mutated mitochondria) might lead to a disease like retinitis pigmentosa, leading to blindness in middle-age, a larger dose might lead to blindness at an earlier age, a still larger dose might lead to early death, while at very high dosage, the mutation might cause stillbirths or miscarriages.
What fascinating stuff! Suddenly, a whole new way by which we think about diseases, their pathology and development has opened up. Very different diseases may actually all arise from the same cause!
How does mtDNA get mutated upon different environmental insults like smoking or drinking polluted water? How do mitochondria compensate for their mutated and less efficient brethren? How do nuclear DNA and mtDNA interact, if at all? And finally, what can we do about mtDNA mutations pharmacologically?
Hopefully we find the answers to these and more questions.
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