Age-Related Mitochondrial DNA Mutation Does Not Appear to Influence Cancer, and Vice Versa

Mitochondria have their own genome, and damage to this mitochondrial DNA is thought to be involved in aging. Some forms of mitochondrial DNA damage can result in mitochondria that are both dysfunctional and have a selection advantage over their unmutated peers, allowing them to overtake a cell, turning it into an exporter of harmful oxidative molecules. Cancer is an age-related condition, in the sense that the risk of suffering cancer grows with age, but this interesting paper provides evidence to suggest that there is little to no mechanistic link between mitochondrial DNA damage and cancer.

Mitochondria are small organelles that play an essential role in the energy production of eukaryotic cells. Here, we analyzed the mitochondrial genomes of 532 whole-genome sequencing samples from cancers and normal clonally expanded single cells. We have shown that the speed with which mitochondria in normal tissues accumulate somatic mutations with age was similar between different tissues. By comparing normal cells with cancer from the same tissue, we have also shown that most mitochondrial mutations in cancer are the result of normal mutagenesis and that treatment perturbations do not strongly impact the mitochondrial mutation load.

In general, cancers and treatment did not have a large effect on the mitochondrial genomes. Chemotherapy, for example, did not result in large observable increases in mitochondrial mutation loads both in vivo and in vitro, even though it can lead to large increases in nuclear mutation loads. This suggests that the relation between cancer and mitochondria is not dependent on mitochondrial mutations. One possible explanation for the limited effect of cancer and its treatments is that the mitochondrial DNA damage they cause might be resolved by cells clearing their damaged mitochondria.