Rockefeller University researchers identify mechanism of cysteine toxicity

Researchers at Rockefeller University have identified the mechanism behind why high levels of the amino acid cysteine are toxic to cells. According to a study published in Nature Metabolism, excess cysteine causes the release of iron from ferritin, the protein complex responsible for safe iron storage.

The released iron enters the mitochondria—the cell's energy-producing structures—where it causes severe damage and leads to cell death. This discovery provides a biological explanation for why cells expend significant energy converting cysteine into glutathione, the cell's primary antioxidant, to keep free cysteine levels low.

Using CRISPR gene-editing technology, scientists identified the SLC25A28 gene, which carries iron into mitochondria, as a key factor in this process. The findings suggest that maintaining low free cysteine levels is an evolutionary necessity to protect the cell's energy generators.