Abstract

LAZAROWSKI, Alberto Jorge; VITALE, Arturo Alberto; AUZMENDI, Jerónimo Andrés  and  POMILIO, Alicia Beatriz. Hierro: desde la homeostasis a la muerte por ferroptosis. Acta bioquím. clín. latinoam. [online]. 2022, vol.56, n.4, pp.490-513. ISSN 0325-2957.

Iron (Fe) is a vital element for almost all organisms due to its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for the proper use of oxygen and energy generation, and its deregulation is related to the processes of oxidative stress and iron-mediated cell death called ferroptosis. Mammalian cells use multiple mechanisms to ensure the acquisition of iron as an essential nutrient, which is normally oxidised in the form of Fe(III) and must be reduced to Fe(II) for adequate intracellular use. Each stage of iron transfer across biological membranes requires a reconversion of its state from oxidised to reduced and vice versa, depending on the metabolic step involved. Distortion of these processes is associated with various diseases, such as iron deficiency due to defects in the acquisition or distribution of the metal that causes anemia, as well as iron overload from excessive iron absorption or defective use, which results in an oversupply of Fe(II) in tissues leading to oxidative damage and cell death. There are multiple regulatory mechanisms that together ensure the balance in iron homeostasis. This update describes the recent advances in the iron regulatory pathways, as well as in the mechanisms underlying iron trafficking from its absorption, mainly biodistribution and its intracellular use, perhaps the most important area where its adequate utilisation or cell death by ferroptosis is defined.

Keywords : Iron; Ferritin; Oxidative stress; Ferroptosis; Neurodegeneration.

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