New study reveals how mitochondrial DNA quality is preserved across generations

Unlike nuclear DNA, which is inherited from both parents and undergoes recombination that can remove mutations, the mtDNA is passed down exclusively from the mother. This makes it vulnerable to the irreversible accumulation of mutations, a process that, over generations, could lead to a mutational meltdown and threaten species survival. To avoid this fate, evolution has equipped cells with two protective mechanisms: a genetic bottleneck, which is a stochastic process that transmits only a subset of all mtDNA copies present in the mother to her children, and purifying selection, which is an active process that weeds out mutated mtDNA molecules as the oocyte develops.

Fewer mitochondrial DNA in the mother – lower mutation burden in the offspring 

Until now, scientists did not know if and how these two processes were connected or how purifying selection worked at the molecular level.

Using mouse models, the researchers discovered that when fewer mitochondrial DNA copies are passed from mother to offspring, there is more genetic variation between individuals and fewer harmful mutations are transmitted. In other words, a smaller genetic bottleneck allows purifying selection to work more effectively, removing defective mtDNA. Conversely, when the researchers disrupted the cell’s ability to recycle damaged mitochondria by impairing autophagy, this protective filtering weakened: harmful mutations accumulated, and mtDNA quality declined.