The importance of iron in pathophysiologic conditions

Biological iron is necessary for vital functions and also potentially toxic to the organisms. This dual effect raised the interest of many investigators to study the mechanisms controlling its homeostasis that are altered in many pathologic conditions. Recently the understanding of iron metabolism significantly improved with the discovery of genes responsible for genetic disorders, such as hemochromatosis, the IRE/IRPs machinery and the hepcidinferroportin axis, which allowed to elucidate the basis of cellular and systemic iron homeostasis. In addition, these advances disclosed a causal link between deregulation of iron homeostasis, inflammation and oxidative stress, often induced by the iron accumulation that is commonly observed in many pathologic conditions. Hence, believing this was time to provide a current state-ofthe-art on the importance of iron in pathophysiologic conditions, we thought to promote a Research Topic with the contribution of top-leading scientists who studied the effects of iron homeostasis disruption on the outcome of genetic, inflammatory, infectious, cardiovascular, and neurodegenerative diseases. Encountering an interest even larger than our ambitions, we successfully collected 42 manuscripts, which cover the major aspects of iron metabolism, from the essential role of iron for cell survival to its contribution in the pathogenesis of various disorders. They have been organized in an e-book in 7 sections. The first section of the Research Topic includes 11 papers that cover the importance of iron in cellular proliferation, differentiation and functioning, and its crucial role in essential processes such as oxygen transport, DNA synthesis, metabolic energy and cellular respiration. They describe the expression and regulation of the main players involved in the mechanisms of iron absorption, recycling, and mobilization (Zhang et al., 2014), the cooperation among different cellular compartments that facilitates iron mobilization/storage and prevents the deleterious effects induced by its accumulation, the role of iron in the Fenton chemistry and its effects on oxidative stress and programmed cell death. Of interest is the study of the different types of circulating iron and the strategies more commonly used for its detection (Cabantchik, 2014). The papers also present updates on iron metabolism in zebrafish, in C. elegans, the role of iron in the skin and the regulatory mechanisms devoted to iron uptake, recycling and mobilization. Altogether they provide the information for a better understanding of the iron involvement in pathophysiologic conditions. The second section includes three papers dealing with the role of heme inside cells and its cytotoxicity when it is released from hemoproteins. In fact, most body iron is contained within the protoporphyrin ring that acts as prosthetic group in many hemoproteins essential to cellular functions. The different aspects related to heme synthesis, intracellular trafficking, scavenging and catabolism are reviewed together with the protective mechanisms that cooperate to prevent the deleterious effects induced by heme accumulation and the pathological conditions in which heme plays a dominant role (Chiabrando et al., 2014). The expressionand regulation ofthemainhemescavengers and transporters identified are also reviewed, together with the notion that maintenance of heme homeostasis is essential to prevent the deleterious effect induced by its overload (Korolnek and Hamza, 2014). The following sections are devoted to describe how disruption of iron homeostasis is associated with a series of syndromes and dictates the outcomes and severity of these disorders.