Work

Tyramine mediates radiation-induced bystander effects

Year: 2026

Type: article

Abstract: Radiation-induced bystander effects (RIBEs) compromise radioprotection and radiotherapy by propagating damage to non-irradiated cells; however, the mediators and underlying circuitry remain incompletely defined. Using localised UV irradiation as the primary experimental system and localised X-ray irradiation as a supportive test in an in vivo Caenorhabditis elegans model, we identify tyramine, a trace amine structurally and functionally related to adrenaline/noradrenaline, as a neuron-derived mediator of RIBEs. Tyramine released from tyraminergic RIM neurons activates TYRA-3, a tyramine-responsive adrenergic-like GPCR related to vertebrate adrenergic receptors. This neuron-to-intestine signal promotes secretion of the insulin-like peptide INS-5, aberrantly engages the DAF-2/insulin signalling pathway (IIS), and triggers endoplasmic reticulum stress, DNA damage responses, and embryonic lethality in non-irradiated tissues. These findings reveal a neuro–intestinal–germline axis that orchestrates RIBEs and uncover an unanticipated role for adrenaline-like signalling. Our work provides a conceptual framework for systematically discovering additional RIBE mediators and identifies pathway components for future evaluation as radioprotective or radiotherapy-modifying targets.

Source: Nature Communications

DOI: 10.1038/s41467-026-78815-z