Key Developments:
- Scientists identify an alternative pathway for cysteine production
- Mice survived despite loss of key cellular reductase systems
- Discovery may reveal a potential weakness in some cancer cells
(ScienceDaily) — September 25, 2026: Scientists have identified a previously unknown cellular pathway that allows mammalian cells to continue producing the essential amino acid cysteine even when the systems traditionally responsible for this process are disabled.
The discovery, led by molecular geneticist Edward E. Schmidt of Montana State University, challenges a long-standing assumption about how cells survive and could eventually help researchers explore new approaches to cancer treatment. The findings were published in Nature Chemical Biology.
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Cysteine plays several important roles in cells, including protein production and protection against cellular damage. Under normal conditions, cells obtain cysteine from cystine by using disulfide reductase systems, particularly thioredoxin reductase and glutathione reductase.
Researchers had considered at least one of these systems necessary for cellular survival. However, experiments involving genetically modified mice showed that liver cells could remain viable even after both systems were disrupted.
"This was supposed to be impossible," Schmidt said, describing the observation that first challenged the prevailing understanding.
The research eventually revealed that the cells can use another chemical route. Instead of reducing cystine's disulfide bond through the usual mechanism, the alternative pathway begins by breaking a carbon-sulfur bond in cystine. This produces cysteine persulfide, which can subsequently generate cysteine through a nonenzymatic reaction. The researchers found that this pathway supplied most of the cysteine in the affected mouse livers.
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The work developed over several years. Schmidt said the initial clue emerged in 2014, when genetically engineered mice survived despite lacking the cellular machinery scientists expected them to need. His team subsequently worked with Peter Nagy and researchers at the Hungarian National Institute of Oncology, along with collaborators from other institutions, to determine how the cells were continuing to produce cysteine.
"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."
According to the researchers, the newly identified mechanism may have an evolutionary connection to cellular defenses against electrophilic toxins. Such compounds can cause chemical stress inside cells, and an additional route for maintaining cysteine production may have helped early multicellular organisms withstand these threats.
The finding could also have implications for cancer research, although the potential application remains at an early stage. Schmidt and his colleagues suggest that some cancer cells may use the same protective pathway to withstand stresses associated with chemotherapy, radiation or immunotherapy.
"This same pathway that protects our cells from oxidants or toxins also likely protects cancer cells from therapies," Schmidt said. He added that understanding the mechanism could eventually allow researchers to investigate whether selectively disabling it in tumors makes cancer cells more vulnerable to existing treatments.
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The study does not establish a new cancer treatment. Rather, it identifies a cellular survival mechanism that researchers may investigate as a possible therapeutic target. Further work will be needed to determine whether the pathway can be safely and selectively manipulated in cancer cells.
The research also involved several Montana State University students. Zoe Seaford and Sydney Austad were co-first authors and conducted research as undergraduates in Schmidt's laboratory, while Martina Serrano Alvarez, Reed Noyd and doctoral researcher Colin Miller also contributed to the work.
The study, titled Cystine C–S bond cleavage fuels cysteine production under disulfide reductase deficiency, was published in Nature Chemical Biology on May 21, 2026, with DOI 10.1038/s41589-026-02213-1.
The latest news coverage of the discovery was released by Montana State University on September 24, 2026. As of September 25, the available reporting reviewed for this update continues to describe the cancer connection as a potential future research direction rather than an established treatment.
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