Posted on behalf of Melissa Lee Phillips.

Cancer researchers got a surprise when they went looking for signs of disease in tumour mitochondria — a surprise that may help to explain the characteristic immortality of cancer cells.

Nuclear DNA in cancer cells is rife with mutations, and there was no reason to think that mitochondrial DNA, which contains genes important for the cell’s metabolism, would be any different. But Jason Bielas and his colleagues at the Fred Hutchinson Cancer Research Center in Seattle, Washington, report in PLoS Genetics this week that far fewer mitochondrial mutations arise in cancer cells than in normal, healthy cells.

Several years ago, Bielas and his co-workers quantified the “mutator phenotype” in the nuclear DNA of human cancers: they found 100 times as many de novo mutations in cancer cells as in healthy cells. Expecting to find something similar in mitochondrial DNA, they measured the frequency of new mutations in the mitochondria genomes of colorectal cancer cells. Instead, they found that the tumour cells contained an average of three times fewer new mutations than normal colon tissue.

The mutations found in healthy cells that seemed to be “missing” from cancer cells were mainly C-G to T-A transitions — a type of mutation that results from oxidative damage. This makes sense, the authors say, because cancer cells are known to shift from an energy metabolism based on oxidative phosphorylation to one based more on anaerobic glycolysis.

In fact, they speculate that tumour cells’ shift to glycolysis may be beneficial to the cancer for just this reason: with an anaerobic metabolism, oxidative damage to mitochondrial DNA decreases; the tumour mitochondria then function better than normal mitochondria, allowing the diseased cells to live indefinitely. This “may be a key factor in cancer-cell immortality”, Bielas says.

The researchers also see potential for new therapeutic approaches in these results. “Cancer therapeutics focused on directly increasing mitochondrial DNA damage might suppress malignant growth,” says Bielas.