In a new Molecular Cell study, a Pitt team has uncovered a novel mechanism by which cells monitor iron availability, with low iron levels stimulating stress signaling pathways to preserve cell fitness. The findings appear to be particularly important in red blood cells, which use large amounts of iron for the oxygen-transporting protein hemoglobin.
“Because iron plays crucial roles in the body, levels must be precisely monitored within cells,” said senior author Shiori Sekine, assistant professor in the School of Medicine and member of the Aging Institute. “Insufficient iron can cause iron deficiency anemia, which is the most common form of anemia worldwide. But on the other hand, excess iron is also toxic to the body. Our study brings attention to an unappreciated iron monitoring system.”
Sekine conducted this study with Yusuke Sekine, assistant professor in the School of Medicine and member of the Aging Institute, and Ryan Houston, their shared laboratory research technician, as well as researchers from the Ludwig Maximilian University of Munich and the National Institute of Neurological Disorders and Stroke.
The researchers showed that mitochondria, the cell’s energy factories, have a special system to monitor cellular iron levels that involves a protein called DELE1. When iron levels are normal, DELE1 is imported into the mitochondria and quickly degraded. But under low iron conditions, DELE1 remains on the mitochondria surface, where it activates cellular stress responses to help blood cells survive under iron-limited conditions.
Their findings shed light on a new role of mitochondria as iron-sensing organelles, which could eventually inform new strategies to treat anemia and other red blood cell disorders.