ROS are evolutionary conserved cell-to-cell signals

Cell-to-cell communication is fundamental to multicellular organisms and unicellular organisms living in a microbiome. A unique cell-to-cell communication mechanism that uses reactive oxygen species (ROS) as a signal (termed the ‘ROS wave’) was recently identified in flowering plants. Here we report that a ROS-mediated cell-to-cell signaling process, like the ROS wave, can be found in ferns, mosses, unicellular algae, amoeba, mammalian cells, and isolated hearts. We further show that this process can be triggered by a localized stress treatment or H 2 O 2 application and blocked by inhibition of NADPH oxidases, and that in unicellular algae, it communicates important stress-response signals between cells. Taken together, our findings suggest that cell-to-cell ROS signaling evolved before unicellular and multicellular organisms diverged. The finding of a ROS wave-like signaling process in mammalian cells further contributes to our understanding of different diseases and could impact the development of new drugs that target cancer or heart disease.