Recent observational and genetic studies have highlighted a potential role for disrupted iron homeostasis in stable and exacerbating chronic obstructive pulmonary disease (COPD). Thus iron deficiency that is not limited to anaemia [1] and single nucleotide polymorphism in the gene encoding iron regulatory protein-2 [2], a key regulatory factor involved in cellular iron turnover and control, hav...

Iron (Fe) is an essential nutrient for plants and although the mechanisms controlling iron uptake from the soil are relatively well understood, comparatively little is known about subcellular trafficking of iron in plant cells. Mitochondria represent a significant iron sink within cells, as iron is required for the proper functioning of respiratory chain protein complexes. Mitochondria are a si...

Iron (Fe) is a double-edged sword for most living organisms. Although it is essential for the catalytic activity of a large number of enzymes, ferrous iron (Fe(2+) ) becomes cytotoxic in the presence of normal respiratory by-products such as H(2) O(2) . Because of this toxicity, intracellular iron concentrations ought to be regulated by elaborated homeostasis systems that, despite decades of ex...

Iron-sulfur (Fe-S) clusters are required for the functions of mitochondrial aconitase, mammalian iron regulatory protein 1, and many other proteins in multiple subcellular compartments. Recent studies in Saccharomyces cerevisiae indicated that Fe-S cluster biogenesis also has an important role in mitochondrial iron homeostasis. Here we report the functional analysis of the mitochondrial and cyt...

The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat's pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular detail...

Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how ...

Disruption of iron homeostasis within the central nervous system (CNS) can lead to profound abnormalities during both development and aging in mammals. The radiation-induced polycythaemia (Pcm) mutation, a 58-bp microdeletion in the promoter region of ferroportin 1 (Fpn1), disrupts transcriptional and post-transcriptional regulation of this pivotal iron transporter. This regulatory mutation ind...

Mammalian iron homeostasis is dominated by the fact that there is no normal excretory route for iron. Iron homeostasis is regulated at the level of intestinal absorption by the body’s demand for iron. In normal adults, iron absorption matches the rate of iron loss due to desquamification or intestinal sloughing. Iron absorption can be increased in response to increased need deriving from events...

Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of genes responsible for iron uptake, release, use, and storage through the actions of the iron regulatory proteins IRP1 and IRP2. However, the manner in which iron levels are sensed to affect IRP2 activity is poorly understood. We found that an E3 ubiquitin ligase complex containing the FBXL5 protein targe...

Intracellular iron homeostasis is critical for survival and proliferation. Lipocalin 24p3 is an iron-trafficking protein that binds iron through association with a bacterial siderophore, such as enterobactin, or a postulated mammalian siderophore. Here, we show that the iron-binding moiety of the 24p3-associated mammalian siderophore is 2,5-dihydroxybenzoic acid (2,5-DHBA), which is similar to ...