IndraLab

Statements

Iron atom inhibits EIF2AK1. 4 / 4
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"In addition to PERK, the eIF2alpha kinase family includes the heme regulated inhibitor (HRI), which is activated by iron or heme deficiency as well as oxidative stress, the general control nonderepressible-2 (GCN2), which is activated by uncharged tRNA caused by amino acid deficiency, and the RNA dependent protein kinase (PKR), which is an interferon (IFN)-inducible protein that becomes activated by binding to double stranded (ds) RNA."
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"Dietary iron repletion completely reversed ID anemia and ineffective erythropoiesis of Hri -/-, eAA and Atf4 -/- mice by inhibiting both HRI and mTORC1 signaling."
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"Indeed, the ISR integrates a range of cellular stresses which activate distinct eIF2α kinases; for example, amino acid deficiency activates GCN2 and ER stress kinase PERK (protein kinase R (PKR)‐like endoplasmic reticulum kinase), while viral or bacterial infection activates protein kinase R (PKR) and iron deficiency activates haem‐regulated kinase (HRI) by 23."
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"At the appropriate heme iron concentrations under normal conditions, HRI function is suppressed by binding of the heme iron."
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