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Cellular iron regulation in animals: need and use of suitable models
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Edité par KIT Scientific Publishing -
As with virtually all biologically essential transition metals, but probably in a more acute way than most, iron excess and deficiency underlie a range of pathological conditions in animals. Accordingly, regulatory systems maintain the proper iron amount to fulfill the needs of the whole body and of each individual cell, while avoiding deleterious effects. The latter may be due to lack of iron availability, e.g. at the active site of iron enzymes, or to reductive catalysis promoted by uncontrolled ferrous ions leading to the formation of reactive species such as the hydroxyl radical. Two major regulators maintain metazoan iron homeostasis, a systemic one relying on the circulating hormone hepcidin, and a ubiquitous cellular one organized around the Iron Regulatory Proteins. These central nodes of iron homeostasis are themselves regulated by numerous effectors beyond iron availability, and they impact other biological processes not directly connected to the use of iron by animal cells. Further, the use of iron resources and conditions impacting it, such as variations of the redox balance, regulate cell fate, e.g. self-renewal of stem cells and differentiation in hematopoiesis. Iron and redox homeostasis are grounded on a series of identified molecular events, but it is not clear how changes of the associated biological parameters may favor proliferation of leukemic clones detrimental to maturation, in acute myeloid leukemia for instance. It now appears that the complex interactions among the networks influencing iron and redox homeostasis should be treated with new integrated data and modeling tools, with the aim to provide a global view of the functional differences between normal and pathological hematopoiesis in particular. The outcomes of the currently on-going efforts in this area are presented herein.
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