Protein kinase activator that acts as a key activator of the integrated stress response (ISR) following various stresses, such as iron deficiency and mitochondrial stress ( , ). Detects impaired protein import and processing in mitochondria, activating the ISR . May also required for the induction of death receptor-mediated apoptosis through the regulation of caspase activation .
Protein kinase activator that activates the ISR in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting DELE1 localization at the mitochondrial surface, where it binds and activates EIF2AK1/HRI to trigger the ISR.
Protein kinase activator generated by protein cleavage in response to mitochondrial stress, which accumulates in the cytosol and specifically binds to and activates the protein kinase activity of EIF2AK1/HRI ( ). It thereby activates the integrated stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha (EIF2S1) phosphorylation, leading to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, the master transcriptional regulator of the ISR (, ).
Subcellular locations: Mitochondrion, Mitochondrion outer membrane, Mitochondrion inner membrane
Imported in the mitochondrial matrix in absence of stress, leading to its degradation by LONP1 . Localizes at the mitochondrial surface in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting localization at the mitochondrial surface and stabilization . Associates with the mitochondrion inner membrane in response to mitochondrial stress, leading to its proteolytic processing by OMA1, and generation of the AP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1) .
Subcellular locations: Cytoplasm, Cytosol
This short form is generated by proteolytic processing by OMA1 in response to mitochondrial stress, leading to translocation to the cytosol.
Detected in liver, skeletal muscle, kidney, pancreas, spleen, thyroid, testis, ovary, small intestine and colon.