| Iron is an essential cofactor in many biological processes. In humans, the daily requirement to maintain normal hemoglobin production in new red blood cells places a special biological demand for iron. The clinical impact of iron deficiency anemia from dietary causes remains a major global public health concern, and acquired and congenital defects in iron metabolism are one of the most common medical diseases. Cellular acquisition of iron in mammalian organisms has been studied intensively and critical genes have been identified. Much less is known, however, about intracellular iron trafficking in the mitochondria, where it is needed, a.o., for the synthesis of hemoglobin. Recently, the first major mitochondrial iron-import carrier essential in hemoglobin synthesis in vertebrate red blood cells, called Mitoferrin (Mfrn), was identified (Shaw GC, et al., Nature 2006;440:96-100). Mfrn belongs to the mitochondrial solute carrier family of proteins and is conserved from yeast to mammals. In zebrafish and the mouse, impairment of Mfrn function leads to severe anemia due to a developmental arrest of red blood cells. The research described in this proposal aims at a detailed insight into the structure-function of the Mfrn protein, which will significantly increase our knowledge of mitochondrial iron trafficking. It will also be directly relevant to our understanding of human disorders involving iron metabolism and red blood cell development. |
