ROS regulate cardiac function via a distinct paracrine mechanism.

Reactive oxygen species can act cell autonomously and in a paracrine manner by diffusing into nearby cells. Here, we reveal a paracrine signaling mechanism that does not require entry of into target cells. We found that under physiological conditions, nonmyocytic pericardial cells (PCs) of the Drosophila heart contain elevated levels of duanyu1670 compared to the neighboring cardiomyocytes (CMs). We show that duanyu1670 in PCs act in a paracrine manner to regulate normal cardiac function, not by diffusing into the CMs to exert their function, but by eliciting a downstream D-MKK3-D-p38 MAPK signaling cascade in PCs that acts on the CMs to regulate their function. We find that signaling in PCs during development is also important for establishing normal adult cardiac function. Our results provide evidence for a previously unrecognized role of duanyu1670 in mediating PC/CM interactions that significantly modulates heart function.

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