Iron is an essential but potentially hazardous biometal. Mammalian cells require sufficient amounts of iron to satisfy metabolic needs or to accomplish specialized functions. Iron is delivered to tissues by circulating transferrin, a transporter that captures iron released into the plasma mainly from intestinal enterocytes or reticuloendothelial macrophages. The binding of iron-laden transferrin to the cell-surface transferrin receptor 1 results in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of haem or iron-sulfur clusters, which are integral parts of several metalloproteins, and excess iron is stored and detoxified in ferritin.
Iron metabolism is controlled at different levels and by diverse mechanisms. The present review summarizes basic concepts of iron transport, use and storage and focuses on the IRE (iron-responsive element)/IRP (iron-regulatory protein) system, a well known post-transcriptional regulatory circuit that not only maintains iron homoeostasis in various cell types, but also contributes to systemic iron balance.
Key words: ferritin, ferroportin, iron-regulatory protein 1 (IRP1), iron-regulatory protein 2 (IRP2), iron–sulfur cluster (ISC), transferrin receptor (TfR).
The IRE-IRP system is a post-transcriptional regulatory circuit that maintains iron homeostasis by controlling the expression of genes involved in iron uptake, storage, and transport. IRP1 and IRP2 bind to IREs in the untranslated regions of their target mRNAs, regulating their stability and translation. IRP1 is primarily involved in iron homeostasis, while IRP2 is more involved in iron storage. The IRE-IRP system is crucial for maintaining iron balance in the body, and its dysfunction can lead to various iron-related disorders, such as hereditary haemochromatosis and iron-refractory iron deficiency anaemia.
The IRE-IRP system is also involved in the regulation of other cellular processes, such as energy metabolism, hypoxic responses, and neuronal function. The system is composed of two main proteins, IRP1 and IRP2, which are involved in the regulation of iron homeostasis. IRP1 is a bifunctional protein that can act as both an iron-sulfur cluster isomerase and an IRE-binding protein. IRP2 is a monofunctional protein that only binds to IREs and does not have any enzymatic function.
The IRE-IRP system is regulated by various factors, including iron levels, cellular redox state, and inflammatory signals. The system is essential for maintaining iron homeostasis in the body, and its dysfunction can lead to various iron-related disorders. The IRE-IRP system is a complex regulatory network that involves multiple proteins and pathways, and itsIron is an essential but potentially hazardous biometal. Mammalian cells require sufficient amounts of iron to satisfy metabolic needs or to accomplish specialized functions. Iron is delivered to tissues by circulating transferrin, a transporter that captures iron released into the plasma mainly from intestinal enterocytes or reticuloendothelial macrophages. The binding of iron-laden transferrin to the cell-surface transferrin receptor 1 results in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of haem or iron-sulfur clusters, which are integral parts of several metalloproteins, and excess iron is stored and detoxified in ferritin.
Iron metabolism is controlled at different levels and by diverse mechanisms. The present review summarizes basic concepts of iron transport, use and storage and focuses on the IRE (iron-responsive element)/IRP (iron-regulatory protein) system, a well known post-transcriptional regulatory circuit that not only maintains iron homoeostasis in various cell types, but also contributes to systemic iron balance.
Key words: ferritin, ferroportin, iron-regulatory protein 1 (IRP1), iron-regulatory protein 2 (IRP2), iron–sulfur cluster (ISC), transferrin receptor (TfR).
The IRE-IRP system is a post-transcriptional regulatory circuit that maintains iron homeostasis by controlling the expression of genes involved in iron uptake, storage, and transport. IRP1 and IRP2 bind to IREs in the untranslated regions of their target mRNAs, regulating their stability and translation. IRP1 is primarily involved in iron homeostasis, while IRP2 is more involved in iron storage. The IRE-IRP system is crucial for maintaining iron balance in the body, and its dysfunction can lead to various iron-related disorders, such as hereditary haemochromatosis and iron-refractory iron deficiency anaemia.
The IRE-IRP system is also involved in the regulation of other cellular processes, such as energy metabolism, hypoxic responses, and neuronal function. The system is composed of two main proteins, IRP1 and IRP2, which are involved in the regulation of iron homeostasis. IRP1 is a bifunctional protein that can act as both an iron-sulfur cluster isomerase and an IRE-binding protein. IRP2 is a monofunctional protein that only binds to IREs and does not have any enzymatic function.
The IRE-IRP system is regulated by various factors, including iron levels, cellular redox state, and inflammatory signals. The system is essential for maintaining iron homeostasis in the body, and its dysfunction can lead to various iron-related disorders. The IRE-IRP system is a complex regulatory network that involves multiple proteins and pathways, and its