Scientists uncover how mitochondria import antioxidants

Many of the processes that preserve us alive additionally put us in danger. The energy-producing chemical reactions in our cells, for instance, additionally produce free radicals—unstable molecules that steal electrons from different molecules. When generated in surplus, free radicals could cause collateral injury, probably triggering malfunctions equivalent to most cancers, neurodegeneration, or heart problems.

Cells resolve this downside by synthesizing antioxidants, compounds that neutralize free radicals. In a brand new examine, Rockefeller scientists establish a key molecule that ferries glutathione, the physique’s main antioxidant, into the cell’s mitochondria, the place free radicals are produced en masse. The discovery, revealed in Nature, opens new prospects for investigating oxidative stress and its damaging results.

“With the potential transporter identified, we can now control the amount of glutathione that enters mitochondria and study oxidative stress specifically at its source,” says Kivanç Birsoy, Chapman Perelman Assistant Professor at The Rockefeller University.

The shuttle into the mitochondria

To keep away from oxidative stress, cells must correctly stability the degrees of free radicals and antioxidants inside their mitochondria, the place power manufacturing occurs. Because glutathione is produced exterior of mitochondria, within the cell’s cytosol, the scientists needed to know the way it will get transported into these tiny powerhouses within the first place.

To make clear this course of, Birsoy’s workforce monitored protein expression in cells in response to glutathione’s ranges. “We hypothesized that glutathione is shuttled by a transporter protein whose production is regulated by glutathione,” Birsoy says. “So if we lower the levels of glutathione, the cell should compensate by upregulating the transporter protein.”

The evaluation pointed to SLC25A39, a protein within the mitochondrial membrane whose operate was hitherto unknown. The researchers discovered that blocking SLC25A39 diminished glutathione contained in the mitochondrion, with out affecting its ranges elsewhere within the cell. Other experiments confirmed that mice can not survive with out SLC25A39. In animals engineered to lack this protein, red blood cells shortly die by oxidative stress because of their failure to deliver glutathione into mitochondria.

The identification of the transporter might result in a greater understanding of a wide range of illness pathways linked to oxidative stress, together with these concerned in growing old and neurodegeneration. “These conditions could potentially be treated or prevented by stimulating antioxidant transport into mitochondria,” Birsoy says.

Moreover, the workforce is now exploring whether or not SLC25A39 may maintain promise as a drug goal for most cancers, by serving to to induce deadly oxidative stress in tumor cells. “In cancer, we would want to prevent antioxidants from getting into mitochondria, and the transporter protein may be our way to do that,” Birsoy says.