New Backup System for Essential Amino Acid Discovered
A cellular "safety net" allows mammalian cells to produce cysteine when their primary systems fail, potentially explaining both how cells survive toxins and how some cancers resist treatment.
Researchers at Montana State University have identified a previously unknown backup mechanism that enables cells to produce the essential amino acid cysteine when the main chemical pathway is disabled. The discovery, led by molecular geneticist Ed Schmidt, was published on May 21 in Nature Chemical Biology.
The Secret: Breaking a Chemical Bond
- Cysteine is vital for building proteins, protecting cells from damage, and maintaining cellular shape through disulfide bonds.
- Cells do not have direct access to cysteine. They must convert its oxidized form, cystine, using a system known as the disulfide reductase pathway.
- Scientists previously believed this conversion process was absolutely essential—that no cell could survive without a functioning disulfide reductase system.
The newly discovered backup works by chemically severing a carbon-sulfur bond in cystine to directly release cysteine.
The Accidental Discovery
The research began in 2014 with a surprising observation: a colony of mice survived despite lacking the known systems to convert cystine to cysteine.
To investigate, Schmidt genetically engineered mice that were missing one or both of the primary disulfide reductases in the liver. For over seven years, his team—in collaboration with Peter Nagy from the Hungarian National Institute of Oncology—worked to uncover the hidden mechanism.
"The ability of our cells to survive, at least for a time, without disulfide reductases, likely evolved in our earliest multicellular ancestors," Schmidt said. "It allowed these organisms to resist being killed by electrophilic toxins."
Why This Matters
This backup system has a double-edged effect:
- For healthy cells: It provides a layer of defense against oxidants and electrophilic toxins.
- For cancer cells: It may help them survive chemotherapies, radiation, and immune therapies.
- For future treatments: Now that scientists know this defense exists, they can target it.
"This same pathway that protects our cells from oxidants or toxins also likely protects cancer cells from therapies," Schmidt explained. "Now that we know they have this defense mechanism, we might be able to precisely disable it in cancers."
The Team
The discovery was significantly advanced by undergraduate researchers:
- Co-first authors Zoe Seaford and Sydney Austad were undergraduate students in Schmidt's lab.
- Additional contributors included undergraduate Martina Serrano Alvarez, doctoral student Colin Miller, and Reed Noyd.
Schmidt joined Montana State University in 1999. His research focuses on gene regulation, metabolism, and mouse genetics.