The iron regulatory proteins: targets and modulators of free radical reactions and oxidative damage.
Iron acquisition is a fundamental requirement for many aspects of life, but excess iron may result in formation of free radicals that damage cellular constituents. For this reason, the amount of iron within the cell is carefully regulated in order to provide an adequate level of a micronutrient while preventing its accumulation and toxicity. A major mechanism for the regulation of iron homeostasis relies on the post-transcriptional control of ferritin and transferrin receptor mRNAs, which are recognized by two cytoplasmic iron regulatory proteins (IRP-1 and IRP-2) that modulate their translation and stability, respectively. IRP-1 can function as a mRNA binding protein or as an aconitase, depending on whether it disassembles or assembles an iron-sulfur cluster in response to iron deficiency or abundancy, respectively. IRP-2 is structurally and functionally similar to IRP-1, but does not assemble a cluster nor exhibits aconitase activity. Here we briefly review the role of IRP in iron-mediated damage induced by oxygen radicals, nitrogen-centered reactive species, and xenobiotics of pharmacological and clinical interest.
Cairo
Gaetano
G
Institute of General Pathology, Cell Pathology Centre CNR, Milano, Italy.
Recalcati
Stefania
S
Pietrangelo
Antonello
A
Minotti
Giorgio
G
D000154:Aconitate Hydratase; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia; D004249:DNA Damage; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D005609:Free Radicals; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000502:physiology*; D035942:Iron Regulatory Protein 2 / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000633:toxicity; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*
D005609:Free Radicals; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2