Heme-regulated eIF2α kinase (HRI) is a protein kinase that plays a crucial role in regulating protein synthesis in response to cellular stress, including hypoxia, oxidative stress, and nutrient deprivation. HRI is activated by the depletion of heme, a key component of hemoglobin and other hemoproteins, and phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), leading to the inhibition of protein synthesis.
The heme-regulated eIF2α kinase (HRI) is an Hsp90 client kinase which, upon folding by Hsp90, will activate, or mature, by autophosphorylation when heme is deficient.
HRI is part of the eIF2α kinase family, which includes other kinases like PERK, GCN2, and PKR, all of which phosphorylate the eukaryotic initiation factor 2 alpha (eIF2α) to inhibit protein translation.
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