Energy can come at a cost. In the body, as energy is produced in our cells, those essential chemical reactions also generate unstable, reactive chemicals called free radicals that can harm other molecules. Excessive free radicals can cause oxidative stress, which may lead to serious health problems like neurodegeneration, cancer, or cardiovascular disease. Antioxidants can help reduce the risk posed by free radicals, and mitochondria, the energy-producers of the cell, have to import antioxidants. Scientists have now learned more about how they do it.
Reporting in Nature, researchers have discovered the role of a crucial molecule called SLC25A39; it ferries an important antioxidant called glutathione into mitochondria.
"With the potential transporter identified, we can now control the amount of glutathione that enters mitochondria and study oxidative stress specifically at its source," said Kivanç Birsoy,an Assistant Professor at The Rockefeller University.
If the balance between free radicals and antioxidants is not maintained, and the reactive radicals gain the upper hand, oxidative stress can occur in cells. But glutathione is produced in the cytosol of cells, so researchers wanted to know how it was getting into the tiny mitochondria.
In this study, the scientists observed protein expression in cells that were exposed to various levels of glutathione.
"We hypothesized that glutathione is shuttled by a transporter protein whose production is regulated by glutathione," said Birsoy. "So if we lower the levels of glutathione, the cell should compensate by upregulating the transporter protein."
This research revealed a protein in the membrane of mitochondria that had a previously unknown function. When the function of this protein, SLC25A39, was blocked, glutathione levels in mitochondria were reduced, though the levels elsewhere remained the same.
When a mouse model was engineered to lack SLC25A39, their red blood cells rapidly died off due to excessive levels of oxidative stress, and an absence of glutathione in mitochondria.
This research may help us learn more about diseases that are associated with oxidative stress, such as diabetes, atherosclerosis, and metabolic disorders. "These conditions could potentially be treated or prevented by stimulating antioxidant transport into mitochondria," Birsoy said.
The scientists are also investigating whether SLC25A39 good act against cancer cells, if it can trigger fatal oxidative stress. It may be possible to kill cancer cells if they cannot import antioxidants into their mitochondria. But any such therapy would have to be directed specifically against those cells.