Why is the chloroplast redox regulatory machinery so complex?

Dithiol-disulfide exchange of cysteine residues has deep effects on protein conformation, hence on enzyme activity, which is the basis of redox regulation. The redox state of cells, including cellular compartments, is dynamically adjusted by reducing, i.e. NAD(P)H, and oxidizing signals, such as reactive oxygen species (ROS), generated during metabolic activity. Among ROS, H₂O₂ triggers the oxidation of cysteine thiols and the formation of disulfide bridges, thus having a relevant contribution to redox regulation. Disulfide reduction is catalyzed by thioredoxins (Trxs), small polypeptides with a characteristic structure, the Trx fold, and an active site formed by the WCGPC motif, or variants of this motif. In heterotrophic organisms, Trxs are reduced by NADPH via an NADPH-dependent Trx reductase (NTR), defining a relatively simple two-component system formed by one or two NTRs and, at most, three Trxs. In contrast, photosynthetic organisms harbor complex redox regulatory machinery. Redox regulation is remarkably complex in plant chloroplasts, organelles equipped with more than 20 Trxs, which rely on two sources of reducing power: photosynthetically reduced ferredoxin (Fdx_RED), via a Fdx-dependent Trx reductase (FTR); and NADPH, the electron donor to NTRC, an enzyme containing NTR and Trx domains, exclusively found in oxygenic photosynthetic organisms. Thus, the long-standing question is why chloroplasts require such complex redox regulatory machinery. Here, we propose a model of chloroplast redox regulation based on the interplay between reducing and oxidizing branches. Moreover, we propose that the complex chloroplast redox regulatory machinery allows the continuous fine-tuning of photosynthetic performance in response to the unpredictable changes of light intensity that plants face in their natural environments.