Ferritin, iron homeostasis, and oxidative damage.
Ferritin is one of the major proteins of iron metabolism. It is almost ubiquitous and tightly regulated by the metal. Biochemical and structural properties of the ferritins are largely conserved from bacteria to man, although the role in the regulation of iron trafficking varies in the different organisms. Recent studies have clarified some of the major aspects of the reaction between iron and ferritin, which results in the formation of the iron core and production of hydrogen peroxide. The characterization of cellular models in which ferritin expression is modulated has shown that the ferroxidase catalytic site on the H-chain has a central role in regulating iron availability. In turn, this has secondary effects on a number of cellular activities, which include proliferation and resistance to oxidative damage. Moreover, the response to apoptotic stimuli is affected by H-ferritin expression. Altered ferritin L-chain expression has been found in at least two types of genetic disorders, although its role in the determination of the pathology has not been fully clarified. The recent discovery of a new ferritin specific for the mitochondria, which is functionally similar to the H-ferritin, opens new perspectives in the study of the relationships between iron, oxidative damage and free radicals.
Arosio
Paolo
P
Dipartimento Materno Infantile e Tecnologie Biomediche, Università di Brescia, Brescia, Italy. arosio@med.unibs.it
Levi
Sonia
S
D000756:Anemia, Sideroblastic / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D005293:Ferritins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005609:Free Radicals; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D005609:Free Radicals; D035925:Iron-Regulatory Proteins; D020033:Protein Isoforms; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron