Scientists working in the only lab at MIT doing hematology research have uncovered a protein that plays a key role in the recycling of iron from blood. Their work, described in the October 11 Journal of Clinical Investigation, could lead to new therapies for certain inherited blood disorders such as beta-thalassemia, a condition that causes chronic anemia.
The team is led by Jane-Jane Chen, a principal research scientist in the Harvard-MIT Division of Health Sciences and Technology (HST).
Two years ago Chen and colleagues showed that a protein, heme-regulated eukaryotic translational initiation factor 2 ±-subunit (eIF2-alpha) kinase, or HRI for short, keeps mice with beta-thalassemia alive. This protein minimizes an abnormal and toxic imbalance of globin chains, the protein base for the hemoglobin found in red blood cells. Hemoglobin carries oxygen to our organs and carts away carbon dioxide waste.
In the new work, the team has found that HRI also plays a key role in the body's iron recycling process. Chen observed that this process falters in mice lacking HRI. As a result, less iron was available for use in the creation of new red blood cells.
A closer look revealed that HRI influences two mechanisms in this recycling process. First, a lack of HRI reduces levels of another protein called hepcidin. Hepcidin, recently discovered to be the master regulator of the iron cycle, releases iron from stores in the body and makes it available to be processed into hemoglobin. Without hepcidin, the body retains iron, but never puts it to work.
The team also found that HRI, which is expressed predominantly in the precursors of red blood cells, is expressed in macrophages. Macrophages are cells that literally reach out and grab dying red blood cells and eat them, digesting them and releasing the iron from their hemoglobin back into the system.