Mitochondrial proteins protect heart cells from chemotherapy damage

Researchers at the University of Illinois Chicago have identified a process by which enzymes can help prevent heart damage in chemotherapy patients. The enzymes are normally found in a cell’s mitochondria. But when heart cells are put under stress from certain types of chemotherapy drugs, the enzymes move into the cell’s nucleus, where they are able to keep the cells alive.

First the team discovered that when the heart cells were stressed by chemotherapy, the mitochondrial enzymes moved into the cell’s nucleus — an unusual phenomenon. But they didn’t know if that movement was the cause of the cell’s damage or the means of its protection, explained Dr. Jalees Rehman, co-senior author.

To find out, the researchers generated versions of the enzymes that would specifically move into the nucleus and bypass the mitochondria. They discovered that this relocation fortified the cells, keeping them alive. They demonstrated that this process worked in both heart cells generated from human stem cells and in mice exposed to chemotherapy.

The discovery suggests new clinical possibilities. Doctors could test individual patients to see if heart cells generated from personalized stem cells would adequately protect themselves from chemotherapy by moving their enzymes from their mitochondria into the cell’s nucleus. They could draw blood from the patient, make stem cells from the blood cells and then use those personalized stem cells to generate heart cells with the same genetic makeup as the patient’s heart cells.

Ref: Nuclear translocation of mitochondrial dehydrogenases as an adaptive cardioprotective mechanism, Nature Communications, DOI 10.1038/s41467-023-40084-5