Mitochondria are “the powerhouse of the cell” (or so any fifth-grade biology textbook will tell you) because they use aerobic respiration to generate ATP, the molecular form of energy that powers cellular processes.
Structurally, mitochondria are unusual in that they have their own DNA. This is because they were initially bacterial cells that were long ago taken over by other cells, giving up their independence for a safe haven and giving their hosts an energy boost in return.
Mitochondrial DNA (mtDNA) codes for many of the proteins required for aerobic respiration, but not all of them. Respiration still requires many proteins encoded by the cell’s normal chromosomes. A new study suggests that the right match between mtDNA genes and chromosomal genes may hold the key to an organism’s health and that some mtDNA may even be beneficial.
This could become a problem because mtDNA mutations have been linked to a number of diseases and mitochondrial replacement has been posited as a means of preventing mitochondrial disease. Such a procedure would create humans containing DNA from three sources: a mother (nuclear DNA), a father (nuclear DNA), and a third person (mitochondrial DNA).
Because this idea is somewhat unprecedented, it has generated some debate, mainly on ethical grounds. The new study suggests it might be worth evaluating the idea on additional medical grounds.
The authors of the paper studied the effects of the mitochondrial-nuclear match by comparing mice with identical nuclear DNA but different mtDNA. This was possible because scientists bred different strains of genetically identical mice, allowing them to match the chromosomal DNA of one strain with the mitochondria of another. These mitochondrial genomes differed by thirty-four bases, a level of variability the authors say is comparable to that seen between African and Eurasian humans.
The research team put the mice through a battery of tests, examining their RNA and proteins they made, plus the chemicals related to their metabolism, then tested their physiological and biochemical functionality. Here you might expect some strange problems, but oddly most of the mtDNA effects seem positive.
The mice with the foreign mtDNA had a longer median lifespan (but not a longer maximal lifespan) and fewer tumors than the mice whose mtDNA matched their mother’s mtDNA. These mice were better able to tolerate the DNA-damaging reactive oxygen species that are a normal by-product of metabolism, and they were better able to regulate their insulin and cholesterol levels. The authors conclude that the new mtDNA “promotes healthier aging” against this chromosomal DNA background.
Of course, that’s just one chromosomal DNA background among those in dozens of different strains of mice. And the article does not address the complex genetic background present in the human population. The main takeaway here is that mtDNA matters. Different variants can affect cellular function and metabolism, which in turn can affect the health of an organism over the course of its life.
Now that we know, it’s probably worth seeing if this can also happen with human mitochondrial transplants.
Nature2016. DOI: 10.1038/nature18618 (About DOIs).