Mitochondria, the power plants of the cell, are the distant descendants of ancient symbiotic bacteria. They contain their own remnant mitochondrial DNA, a small genome distinct from that in the nucleus. This DNA is, unfortunately, less well protected and repaired than is the case for nuclear DNA. It can suffer forms of mutation that cause a mitochondrion to be both dysfunctional and able to resist the quality control mechanism of mitophagy that is responsible for removing damaged mitochondria. Since mitochondria reproduce by replication, this can lead to cells quickly overtaken by broken mitochondria, which in turn pollute the surrounding tissue with damaging oxidative waste products.
As is true for most low level causative mechanisms of aging, it is an open question as to the relative importance mitochondrial DNA damage in the progression of aging, when compared with other known forms of molecular damage. Mitochondrial dysfunction is implicated in many age-related conditions, and in differences in species life span. The ability to measure mutational rates in specific tissues is a necessary step on the way to a better understanding the importance of this process in age-related disease and loss of function.
Researchers used an extremely accurate DNA sequencing method to sequence the entire genome of mitochondria - organelles that are the powerhouse of the cell - in both reproductive cells and other cells in the body and showed that, depending on the cell type, ten-month-old mother mice had approximately two-to-three times more new mutations than their nearly one-month-old pups.
The study is the first to directly measure new mutations across the whole mitochondrial genome in reproductive cells. "Previous studies identified new mutations by comparing DNA sequence between parents and offspring, rather than looking directly at the reproductive cells. This could provide a biased picture of the rate and pattern of new mutations, because selection could prevent some mutations, for example those that are incompatible with life, from ever being seen."
When the team compared the mitochondrial genome sequences of the mother mice and their pups, they found an increase in the number of mutations in the older mice for all of the tissues that they tested. This suggests that as the mice age, their mitochondrial genomes accumulate mutations, so the team wanted to know if they could identify the source of these mutations. Mutations can occur because of errors in DNA replication when a cell divides and makes copies of its genetic material for each of the resulting daughter cells. They can also be caused by environmental factors like UV light or radiation, for example, or if there are errors during DNA repair.
"When we looked at the pattern of mutations in the mitochondrial genomes it fit with what we would expect for most of them occurring through replication errors. But we also observed some differences in the mutation patterns between oocytes and body cells. This suggested that the contribution of different molecular mechanisms to mitochondrial mutations varies among these cells. Given that they undergo different numbers of cell divisions, it makes sense that the contribution of various mechanisms to the mutation process might be different between the tissues. However, because we see some evidence of replication error mutations in the mitochondrial genomes of oocytes as well, it's possible that there is turnover of mitochondrial genomes in oocytes even though the cells are not dividing themselves."