While reactive oxygen species (ROS) have long been known to drive aging and neurodegenera-tion, their persistent depletion below basal levels also disrupts organismal function. Cells counter-act loss of basal ROS via the reductive stress response, but the identity and biochemical activity of ROS sensed by this pathway remain unknown. Here, we show that the reductive stress E3 ligase CUL2FEM1B specifically acts at mitochondrial TOM complexes, where it is regulated by ROS that are produced as byproducts of complex III of the electron transport chain (ETC) during oxidative phosphorylation. By modulating localized CUL2FEM1B activity, ROS tune protein import into mitochondria and thereby control the abundance of the rate-limiting ETC complex IV. As complex III yields most ROS when the ETC outpaces metabolic demands or oxygen availability, our findings identify basal ROS as sentinels of mitochondrial activity that help cells adjust their ETC to fluctuating environments, as required for cell differentiation and survival.