In cells under attack, mitochondria can act as sentinels, revving up the repair apparatus deep inside the nucleus to protect the cell’s primary genetic cargo.
Mitochondria, the cell’s energy-making structures, contain DNA distinct from that in the nucleus. To explore how mitochondria communicate with the nucleus, Gerald Shadel at the Salk Institute for Biological Studies in La Jolla, California, and his colleagues dosed cells with the cancer drug doxorubicin, which damages DNA. The cells’ mitochondrial DNA alerted the nuclear DNA, which activated a repair protocol.
The team altered melanoma cells to prompt their mitochondria to release more DNA. When these cells were implanted into mice, they produced tumours that survived doxorubicin treatment better than standard melanoma tumours.
The scientists also put the mitochondria of engineered mice on alert and dosed these mice with ionizing radiation, which is another cancer treatment. The engineered mice showed signs of more vigorous nuclear repair in their spleens than control mice.
The results show that when damaged by a toxin or other form of abuse, the abundant mitochondrial DNA warns the nucleus that an attack is underway. This surveillance system might explain how cells acquire resistance to some DNA-targeting cancer drugs.