Is ascorbic acid a key signaling molecule integrating the activities of 2-oxoglutarate-dependent dioxygenases? Shifting the paradigm

The integration of different environmental cues and the harmonization of proper responses require molecular communication at different levels. Enzymes belonging to the large superfamily of 2-oxoglutarate-dependent dioxygenases (2-ODDs) use for their catalytic activity different cofactors, including molecular oxygen, 2-oxoglutarate, and ascorbic acid (ASC). In plants, 2-ODDs are involved in the synthesis of hydroxyproline (largely present in cell wall proteins), gibberellins, ethylene, zeaxanthin, and many more relevant molecules. In addition, 2-ODDs operating in the epigenetic control of gene expression by regulating cytosine and histone methylation have been recently identified in both animals and plants. It is here hypothesized that each of the co-substrates required for the complex catalytic mechanism of 2-ODDs provides specific molecular information. Such information is integrated by 2-ODDs, which in turn regulate the synthesis of information-bearing metabolites (e.g. hormones), and control epigenetic processes. The evolutionary success of the catalytic mechanism shared by 2-ODDs is possibly related to the parallel activation of different biosynthetic pathways.