Iron Homeostasis in Health and Disease

Abstract

Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe-dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload.

Brain iron concentrations in regions of interest and relation with serum iron levels in Parkinson disease

“…In example, dopaminergic cell death precedes iron deposition in animals treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [42]. Abnormally high levels of brain iron are observed not only in PD, but also in other neurodegenerative diseases such as in the genetic syndromes of neurodegeneration with brain iron accumulation (NBIA) [43, 24]. Several genetic causes have been recently identified for various forms of NBIA, and the mutations functionally characterized.…”

Benzoate and Sorbate Salts: A Systematic Review of the Potential Hazards of These Invaluable Preservatives and the Expanding Spectrum of Clinical Uses for Sodium Benzoate

“…Hippurate is reported to impair basal and insulin-stimulated glucose uptake into cells in culture (Spustova and Dzurik 1991). Individuals with genetic defects in the genes of iron homeostasis (hereditary hemochromatosis) (Gozzelino and Arosio 2016;Guo and others 2016) or with Alpers-Huttenlocher syndrome (Komulainen and others 2015) are especially susceptible to ROS-induced damages. For them, the capacity of sorbate and benzoate to enhance mitochondrial ROS production may be a concern, as shown for genetic defects in the maintenance of human mtDNA integrity causing a sensitization to sodium valproate others 2009, 2011).…”

Proteínas relacionadas con el metabolismo del hierro corporal

“…La FLVCR1a es importante para la formación esquelética y la integridad vascular y la FLVCR1b evita la acumulación de hemo durante la eritropoyesis fetal. El hemo es fundamental para diferentes procesos celulares pero su exceso es tóxico para la célula, causa estrés oxidativo y daño a membranas, por lo tanto, la expresión y funcionalidad de estas proteínas es esencial para su homeostasis (97).…”