**7. A rewarding double play: the two faces of AsA**

A continuing challenge for all organisms is the real-time adaptation to ever-changing environmental conditions. Specific external/internal cues must be sensed, and the resulting signal transduced to the corresponding response regulator. For example, in two-component systems, observed in bacteria and several eukaryotes, but not in humans, the signal is transduced by a chain of phosphorylation events [90]. Another common form of signal transduction is ensured by redox regulation using thiol-disulfide exchanges [91, 92]. In both cases, the signal is rapidly and efficiently transduced to a transcriptional regulator activating some general and some specific responses in a cascade mechanism. Many stress and pathological conditions induce ROS production, but different forms of stress, or their combination, result in distinct signatures of ROS levels [93], increasing the specificity of the response.

AsA is oxidized by the direct interaction with ROS and, in plants, also by the reaction catalyzed by AsA peroxidases. In stress conditions, when high ROS production occurs, AsA is converted to its oxidized form dehydroascorbic acid (DHA) via the dismutation of the short-lived ascorbate free radical (AFR, also known as monodehydroascorbate) [94]. The more AsA is oxidized, the less AsA is available for the reactions catalyzed by 2-ODDs. This is indirectly confirmed by the observed correlation between the inactivation of some 2-ODD coding genes and higher AsA content in *Arabidopsis* insertion mutants [95]. In this perspective, AsA is at the same time the sensor of stress conditions and the activator of downstream responses via 2-ODDs. In other words, AsA antioxidant function, rather than just a way to remove ROS, should also be considered the first step in the activation of a multi-directional signaling module.
