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Comment by aurizon | Hacker News Reader

Some longevity researchers could investigate the DNA sequence of the mitochondrial DNA(a discrete object) to see if there is a length of life correlation = CRISPR edit towards longer life. It would be easily explored in mice and then there could be some edits in an egg very soon after fertilisation to replace that mitochondrial DNA in that egg to see the result. Might be a hard task to find/replace all these mitochondria and maintain life? In a single mouse egg = how many are there? A search finds this interesting paper = a good rabbit hole indeed. It is an area of intense research. https://pmc.ncbi.nlm.nih.gov/articles/PMC4684129/

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We are not able to modify human mitochondria other than with TALENs or ZFNs - CRISPR doesn't work (can't import the sgRNA). Even that doesn't work that well. We have not been able to genetically transform human mitochondria. It's a big open question of how we could do it. In yeast you use a gene gun because they can actually survive it, and even that is exponentially harder than normal yeast engineering.

Hundreds to thousands of mitochondria per cell. They also encode pretty few genes, and those genes are mainly there because they directly get injected into the membranes. There are like a thousand mitochondrial genomes per nuclear genome, each with only ~10 genes that repair each other, while the nucleus has literally thousands of mitochondrial genes in two copy. Much easier to look at that

I see, your knowledge far exceeds mine in this arena. Yes, I knew they encoded few genes. Makes me wonder if they could be built in a protein shop (if even they knew how it rolled and folded in volume after editing in the longer life or higher energy genes from ?? That said, it must be highly conserved = hard job, as the conserving mechanism could resist by back editing??

They're kinda a built-in protein shop (got their own ribosomes) - but they're only for 1 thing, which is locally regulating the insertion of extremely hydrophobic proteins for respiration. You could imagine that this one application (maintaining and repairing membrane potential) requires MAXIMUM performance and response (they gotta be JIT-ed into the membrane), so much that the cell maintains thousands of genes for those ~13 genes to be able to be expressed, and it is totally worth it. Everything else gets moved to the genome. It's like we have tiny virtual machines that we can scale to respire more.

Chloroplasts are a more interesting example of a protein shop. RuBisCO, for example, the most abundant protein on earth, is coded in chloroplasts to scale expression. It is mainly there for dynamic scaling purposes, whereas the mitos are very optimized for one thing

Mitochondria don't go back because if there is 1000 mt genomes to 1 nuclear genome it is extremely energetically desirable to have 1 copy rather than 1000 copies of any given gene.

Yes, googled it. A hugely replicated one trick cowboy made to perform on cue. RuBisCo = a deep rabbithole indeed. https://www.youtube.com/results?search_query=RuBisCO Thanks, as a casual reader I appreciate explanations from someone like you!!

There are ~100,000 mitochondria in a human egg cell-- I think that's a pretty tall order.

Yes, I suspect is starts with extra metabolic capability = greater need for the task it is being prepared for. Since women have all their oocytes from an early age - speculating they might mature for fallopian release, and in that maturation mitochondrial proliferation occurs? Alternatively this might occur at puberty with hormonal triggering oocytes in some sequential manner as evolutionary efficiency might be a 'just in time' process?

It's doable https://www.nature.com/articles/s41467-022-33530-3

100,000 x 6kbp == 600 million, or less than 1/5 of our genome. Difficult part is the barcoding bits, but that is not THAT hard.

reading them would be hard enough, but editing them seems pretty darn hard.

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