CHARACTERIZATION OF THE NEWLY DISCOVERED MITOCHONDRIAL FERRITIN: IMPLICATIONS FOR FRIEDREICH’S ATAXIA, SIDEROBLASTIC ANEMIA AND DISORDERS WITH MITOCHONDRIAL IRON LOADING

We have recently identified a new form of ferritin that is specifically addressed into the mitochondria. This is structurally ad functionally related to the well characterized cytosolic ferritin that has a major role in the regulation of cellular iron homeostasis and in the protection against oxidative damage. It acts by removing and incorporating in its large cavity the iron potentially toxic for its ability to catalyze the formation of free radicals. Mitochondria are exposed to reactive oxygen species that easily react with the iron transiting for the synthesis of heme and Fe/S clusters, thus producing toxic free radicals. Our working hypothesis is that the mitochondrial ferritin protects the organelle from this reaction and may have a major role in the genetic pathologies associated to mitochondrial iron overloads, such as Friedreich ataxia and sideroblastic anemia. We propose to produce reagents and model cellular systems to characterize the functional and biological properties of this new ferritin with the hypothesis that this leads to a better understanding of mitochondrial iron homeostasis, presently obscure. In addition, we plan to use the ferritin as a probe to study how iron enters and leaves the organelle to gather information useful for the development of new therapeutic strategies to reduce mitochondrial iron excess which causes cellular damage in the two pathologies.