Why Glutathione Matters

Glutathione is well known outside of cancer research. It reduces oxidative stress, helps detoxify harmful substances, and supports the immune system. But inside cancer cells, researchers found that mitochondrial glutathione is doing something very different.

The team, led by Dr. Kivanç Birsoy, showed that breast cancer cells with higher levels of mitochondrial glutathione were more likely to spread to the lungs. They confirmed this by using advanced imaging tools to track glutathione levels in both tumors and lung tissue.

The key transporter behind this effect is a protein called SLC25A39, which moves glutathione into mitochondria. Without it, cancer cells struggled to survive in new tissues.

How It Fuels Cancer Spread

The big surprise?

Glutathione wasn’t acting as an antioxidant here. Instead, it worked as a signal that switched on ATF4, a stress-response protein that helps cancer cells adapt when oxygen is low—precisely the kind of stressful environment they face in a new organ.

This made mitochondrial glutathione especially important during the early stages of metastasis, when cancer cells first try to take root in another part of the body.

Dr. Birsoy’s lab had already made breakthroughs with SLC25A39.

In 2021, they proved it was the transporter that carries glutathione into mitochondria. In 2023, they showed that it also acts like a sensor, adjusting how much glutathione gets inside. So when this same transporter popped up in cancer studies, the team already had the tools to dig deeper.

They also found that patients with breast cancer that had spread to the lungs showed higher levels of SLC25A39. Even more concerning, patients with more of this transporter tended to have worse survival rates.

What This Could Mean for the Future

One day, drugs designed to block glutathione’s entry into mitochondria might help prevent the spread of breast cancer. Unlike treatments that shut down entire cell systems, this approach would be more targeted, potentially offering fewer side effects.

For now, the team’s work highlights the need to study metabolism not just at the whole-cell level but inside specific compartments like mitochondria. As Dr. Birsoy explained, “We need to look at organelles closely to understand how metabolites influence human health.”