Iron uptake, utilization and storage in mice

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Iron uptake, utilization and storage in miceTotal iron deficiency is incompatible with life, whereas iron excess is dangerously toxic. Thus, body iron levels in mammals are tightly maintained in balance. Iron metabolism is regulated such that sufficient iron is provided for body needs (to virtually every cell and, in particular, red blood cells), but at the same time avoiding its toxicity through safe storage in specialized molecules, because free iron can participate in the formation of free radicals. Because iron absorption from the intestine is insufficient to meet daily erythroid demands,iron-recycling and re-utilization constitute important aspects of iron homeostasis. The cells responsible for efficiently recycling iron belong to the mononuclear phagocytic cells, which includes macrophages. One compartment in which tissue turnover is critical is the hematopoietic system. In the adult mouse, about 22 million lymphocytes are produced daily and, for their number to remain constant, an equal number of cells must die every day. However, practical and sensitive tools necessary to study temporal and spatial changes in tissue iron content are currently lacking.Overall, we aim to understand how cells and organisms regulate their iron content, and how distinct tissues coordinate iron distribution in response to altered iron homeostasis.We propose to unravel several essential aspects ofiron homeostasis: the regulation of cellular iron uptake and recycling, intestinal iron absorption, and brain iron metabolism. We expect that this fundamental research will make significant contributions to the field of iron biology and animal physiology. Because iron metabolism shares remarkable similarities in mammals and iron is essential for biological systems, the knowledge gained by studying iron metabolism in mice may very well become pertinent to more applied fields, such as human health and animal husbandry.