How Cell Metabolism Adjusts to Iron Deficiency

Researchers have found that when faced with iron deficiency, cells can reprogram their metabolism to reduce the production of iron-requiring proteins.

Investigators at Duke University (Durham, NC, USA) used the yeast Saccharomyces cerevisiae as a model representing human cells. The yeast was grown in media containing a limited concentration of iron, and the effect of restricted iron availability on the cell's genetic machinery was determined.

The investigators found that under low iron conditions the yeast over-produced Cth2, an RNA binding protein. The increased activity of Cth2 interfered with the production of proteins that require iron to function. In a paper published in the January 14, 2005, issue of Cell, the investigators reported that Cth2 inhibited more than 80 genes.

"We discovered that iron deprivation actually reprograms the metabolism of the entire cell,” said senior author Dr. Dennis J. Thiele, professor of pharmacology and cancer biology at Duke University. "Literally hundreds of proteins require iron to carry out their proper function, so without this nutrient, there is a complete reorganization of how cellular processes occur. Current diagnostic markers for iron deficiency are not very sensitive, unless the deficiency is severe. Pinpointing the genes affected by iron deprivation should provide us with a genetic fingerprint of what patients with varying levels of iron deprivation look like.”