A study published Aug. 14 in the journal Cell reports that small molecules called polyamines help keep iron inside cells in a non-reactive state, functioning like storage lockers until the metal is needed. The work was described in a report published Aug. 25 by MIT, whose researchers Ankur Jain, Whitney Henry and Pushkal Sharma conducted it with the Whitehead Institute for Biomedical Research and the Koch Institute for Integrative Cancer Research. Polyamines are among the most abundant small molecules in cells, at levels comparable to ATP.

Using a genome-wide genetic screen, the team found that when polyamine levels were reduced, the protein GPX4 became essential for cell survival, and cells had more of a protein that stores iron in mineralized form. The researchers then paired a new fluorescent sensor for chemically reactive iron with an earlier sensor for polyamines and observed that as polyamine levels dropped, reactive iron rose.

The authors suggest the findings could inform cancer treatment strategies that combine drugs lowering polyamines with GPX4 blockers, and could offer clues about early-onset Parkinson's disease, in which mutations affect polyamine transport. They describe these as possible future directions; the work is preclinical and does not establish clinical outcomes. The new sensor may also aid research on aging, cancer and neurodegeneration. Funding came from the National Institutes of Health, the Bumpus Foundation and the Pew Charitable Trusts.