Mitochondrial diseases don't seem like an easy target because they are really metabolic and homeostatic disorders, which are very complex. If the main failure of mitochondrial disorders were a lack of energy production, how could cancer cells grow faster than regular cells, yet turn off mitochondrial energy production in favor of anaerobic glycolysis and lactic acid fermentation (which is much less efficient)? Mitochondria have an under appreciated role in ion homeostasis, intermediary metabolism, and biosynthesis that seems to be the cause of many mitochondrial diseases. The mitochondrial genome only codes for a few proteins, but relies heavily on the nuclear genome for proteins. In other words, the mitochondria isn't just an isolated power plant; it's an integrated system that provides power in addition to logic, material processing, signaling, etc. Sorry to hear about your disorder, fortunately there are people researching these diseases.
Well said, I thought HN were only for geeks, but you clearly have a solid biology background.
I agree that faulty mitochondria will break homeostasis and from this point on, the problem is unsolvable.
But homeostasis will break because:
1. Plain vanilla energy deficit. Not enough energy. Babies die within the first days after birth.
or
2. Inefficient - but normal - energy production. This will produce an excess of free radicals, "emitting" all kinds of weird signals to the rest of the cell/tissue/body. Most of mitochondrial diseases and diseases that cause a secondary mitochondrial dysfunction fall in this category. "The threshold effect" - mutant mitochondria outnumber healthy mitochondria as you grow older - will eventually take you to point 1.
Given this, repairing the mitochondria will bring homeostasis back. Currently, there are 3 lines of thought:
1. Repair the faulty mitochondria
2. Allotopic expression (literally, make backup copies of mitochondria DNA in the nuclear DNA and let them "express" from here instead of from mtDNA)
3. Kill faulty mitochondria. Given that mitochondria go through a fusion/fission cycles every few days, killing faulty mitochondria will restore a healthy mitochondria population in a very short period. The underlying genetic defect is still there, but it causes no harm at all.
Thanks for your concert. I didn´t want to be tragic in my original post. My life depends on my mitochondria, but I am doing relatively well considering my disease.
For the curious, I have CPEO + myopathy, common mtDNA deletion, 35% mutation load.
I think emerging research in genome engineering and sculpting evolutionary fitness using genome engineering tools will probably solve these disorders. However, these technologies have--in my opinion--lower hanging and more profitable fruit in other biomedical interventions, such as cancer therapy. They will probably cure mitochondrial disorders as a side-effect, though, and possibly by small start-ups (since there's such little money in these rare, one-shot-cure diseases).
Could you point at a high quality reputable paper saying "as low as 1:1,000"? Did you mean 1 in 1000 people with disease have a mitochondrial cause, or 1 in 1000 people have a mitochondrially caused disease?
