This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Cysteine is one of the main building blocks that cells use to make proteins. But this amino acid is a double-edged sword—too much cysteine is toxic to the cell.
Cells therefore keep free cysteine levels to a minimum, converting most of the amino acid into the antioxidant glutathione. Now, a new paper explains why cysteine is so toxic at high concentrations. The findings, published in Nature Metabolism, show that cysteine can pry iron from ferritin, the protein complex that normally keeps the metal safely locked away, flooding the cell with iron that accumulates in the mitochondria and leads to cell death.
These results resolve a longstanding question in basic biology and offer the first comprehensive explanation for why cells may have evolved to expend significant energy packaging cysteine into glutathione. "Throughout evolution, our cells preferred glutathione as their primary redox molecule," says Kivanç Birsoy, head of the Laboratory of Metabolic Regulation and Genetics at Rockefeller. "If cells had relied on cysteine instead, it would have been catastrophic for mitochondria.
We now know that keeping free cysteine low was nature's way of protecting the cell's energy generator." Cysteine presents cells with something of a biochemical dilemma. On one hand, the cell needs cysteine. It's one of only 20 amino acids used to build proteins, and it contains a sulfur-containing chemical group that makes it unusually reactive and useful for maintaining proteins and controlling the cell's chemical environment.
Cysteine is also needed to build iron-sulfur clusters, which help many proteins do their jobs, and to generate glutathione, the cell's primary antioxidant. When cells have too little cysteine, glutathione becomes depleted, ultimately triggering cell death. On the other hand, too much cysteine is just as toxic.
In fact, cysteine is the only one of the 20 protein-building amino acids that becomes acutely toxic when present in excess. "There are some studies suggesting cysteine supplementation might be beneficial," Birsoy says. "This should be taken with a grain of salt precisely because of how toxic high cysteine is to cells." Cells therefore keep free cysteine at very low levels, rapidly converting it into glutathione, which they can safely maintain at much higher concentrations.
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