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: Iron is essential. Our cells need it to produce energy, carry oxygen throughout the body and power countless chemical reactions that sustain life.
But this metal has a dark side. When too much of it is left free inside cells, it can trigger destructive reactions that break down DNA, proteins and even cell membranes. Now, Whitehead Institute Member Ankur Jain, former postdoc Whitney Henry and graduate student Pushkal Sharma have discovered that cells rely on an unexpected protector against this threat: small molecules called polyamines.
The researchers' detailed findings, published in the journal Cell, reveal that polyamines act like storage lockers for iron, safely holding the metal in a nonreactive state until cells need it. These findings solve a decades-old mystery about why cells maintain such extraordinarily high levels of polyamines and uncover a previously unknown defense mechanism that protects cells from toxic iron overload. This work could also help scientists develop better cancer treatments by allowing iron overload to trigger cancer cell death.
It could also offer new clues about diseases like early-onset Parkinson's disease, in which mutations affect polyamine levels within neurons. The Jain Lab studies RNA, the intermediary between DNA and the tiny molecular machines called proteins that perform most of the essential tasks inside cells. The lab is particularly interested in how RNA folds, misfolds and sometimes clumps inside cells.
Jain and Sharma first began studying polyamines because these molecules bind to RNA and help shape its structure. However, they suspected that polyamines must be playing other roles inside cells: They're among the most abundant small molecules within cells, present at levels comparable to ATP, the molecule cells use as their energy currency. "We've known that without polyamines, cells stop growing and dividing," says Jain, who is also an associate professor of biology at the Massachusetts Institute of Technology (MIT).
"But their best-known function only requires a small fraction of the polyamine levels cells actually have." To uncover polyamines' hidden function inside cells, the researchers used a large-scale genetic approach that allows them to screen the entire genome at once, rather than testing genes one by one, to find out which cellular processes are affected when polyamine levels are changed within cells. The screen revealed that when cells have reduced levels of polyamines, a protein called GPX4 becomes essential for survival. GPX4 is known to prevent harmful chemical reactions that damage the fatty molecules that make up cell membranes.
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