An ancient mitochondrial program tunes translation to haem availability.

Mitochondrial haem scarcity is detected by an ancient OMA1-DELE1 pathway that regulates translation during erythroid development, conserved across species including invertebrates.

• Why it matters: Understanding how cells monitor and respond to haem levels is crucial because haem imbalance causes anemia and related diseases, yet the molecular sensing mechanisms are poorly understood.
• What they did: The study used molecular and pharmacological approaches to show that haem deficiency activates an OMA1-DELE1 axis in mitochondria, which then modulates HRI kinase activity across human tissues and invertebrates.
• The result: This discovery reveals a primordial haem-sensing system that prevents toxicity and offers potential for therapies, such as increasing fetal globin expression in haemoglobinopathies.