negative regulation of iron ion transmembrane transport

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of iron ions from one side of a membrane to the other by means of some agent such as a transporter or pore. [GOC:mah]

Negative regulation of iron ion transmembrane transport refers to the cellular mechanisms that control the movement of iron ions (Fe2+) across cell membranes. This is a tightly regulated process as iron is essential for many vital cellular processes, including oxygen transport, DNA synthesis, and energy production. However, excessive iron accumulation can be toxic, leading to oxidative stress and damage.

The negative regulation of iron ion transmembrane transport involves a complex network of proteins and signaling pathways that work together to maintain iron homeostasis. Key players include:

* **Hepcidin:** A hormone produced by the liver that acts as a master regulator of iron absorption. Hepcidin binds to the iron exporter protein ferroportin, leading to its internalization and degradation. This reduces iron export from cells and limits iron absorption in the gut.
* **Transferrin receptor 1 (TfR1):** A protein that binds to transferrin, the main iron carrier in the blood, and facilitates iron uptake into cells. When iron levels are high, TfR1 expression is downregulated, limiting iron uptake.
* **Divalent metal transporter 1 (DMT1):** A protein that transports iron from the gut lumen into enterocytes and from endosomes to the cytoplasm. Its activity is regulated by iron levels and other factors.
* **Ferroportin:** An iron exporter protein that mediates the release of iron from cells into the bloodstream. Its activity is negatively regulated by hepcidin.
* **Iron regulatory proteins (IRPs):** These proteins bind to iron response elements (IREs) in the mRNAs of iron-related proteins, such as TfR1 and ferritin. When iron levels are low, IRPs bind to IREs, stabilizing TfR1 mRNA and preventing ferritin mRNA translation. This leads to increased iron uptake and decreased iron storage.

**Regulation mechanisms:**

* **Iron levels:** Iron levels are the primary regulator of iron transport. When iron levels are high, hepcidin production increases, leading to decreased iron absorption and export. Conversely, when iron levels are low, hepcidin production decreases, allowing for increased iron absorption and export.
* **Inflammation:** Inflammatory signals can also stimulate hepcidin production, reducing iron availability for pathogens.
* **Erythropoiesis:** The production of red blood cells (erythropoiesis) requires a large amount of iron. Therefore, erythropoietic signals can suppress hepcidin production, increasing iron availability for red blood cell formation.
* **Other factors:** Hormones like erythropoietin and growth factors can also influence iron transport.

**Disruption of this regulatory network can lead to iron deficiency (anemia) or iron overload (hemochromatosis).** Understanding the mechanisms involved in negative regulation of iron ion transmembrane transport is crucial for developing strategies to treat these disorders and maintain iron homeostasis.'
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Proteins (1)

Compounds (2)