Ancient mitochondrial relay links haem availability to translation via DELE1–HRI

A mitochondrial haeme-sensing pathway, mediated by OMA1 and DELE1, senses haem deficiency and promotes haem release from the HRI kinase in the cytosol, activating translation control via the ISR. This ancient signaling axis operates across human tissues including erythroid progenitors, is conserved back to simple organisms, and pharmacological manipulation of the pathway can boost fetal globin expression, suggesting new therapeutic angles for haemoglobinopathies.