A molecular geneticist at Montana State University has discovered a cellular process previously believed impossible: the creation of the amino acid cysteine within a living cell when the cell's primary systems to do so fail. The discovery, announced on June 12, may one day lead to new cancer treatments.
The findings were published May 21 in the scientific journal Nature Chemical Biology. Ed Schmidt, professor of genetics and development in the Department of Microbiology and Cell Biology at MSU's College of Agriculture, is the lead author. "All cells need a constant supply of an amino acid called cysteine in order to stay alive," Schmidt said. "Yet cysteine is not available outside of the cells."
Cysteine plays a critical role in building proteins and defending against damage by enabling formation of disulfide bonds that stabilize protein structures. For decades, researchers have known that cells must create cysteine internally by chemically splitting its oxidized form—cystine—using what is called a disulfide reductase system. "Scientists long believed this process was absolutely essential for all living cells," Schmidt said. "However, we have discovered a previously unknown system in mammalian cells that can take over when the main systems fail."
Schmidt described how his team made this discovery over nine years, beginning with genetically engineered mice lacking both primary disulfide reductases in their livers that survived despite scientific expectations they would not be able to produce cysteine without these systems. He said, "This was supposed to be impossible... No living organism or cell had ever been found that could live without having a functioning disulfide reductase system." Further research with Peter Nagy from the Hungarian National Institute of Oncology revealed that when traditional pathways are unavailable, a backup system severs an adjacent carbon-sulfur bond in cystine to release usable cysteine.
This alternative pathway may help humans survive exposure to electrophilic toxins found naturally or environmentally and might also help some cancer cells resist therapies such as chemotherapy or radiation treatment. "This same pathway that protects our cells from oxidants or toxins also likely protects cancer cells from therapies," Schmidt said. "Now that we know they have this defense mechanism, we might be able to precisely disable it in cancers, making them more susceptible to cancer therapies as well."
Several students coauthored the paper alongside collaborators from other institutions involved throughout various stages of research on this project since its inception.
