The molecular language of cells

Cells have evolved complex molecular networks that enable them to survive and adapt to diverse environmental challenges. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) act as signalling molecules to outside cues and elicit specific responses.

ROS/RNS mainly lead to post-translational modifications on proteins, namely nitrosylation, disulphide bond formation and glutathionylation, which in turn affect numerous fundamental cell processes. The pattern of redox-based protein modifications likely constitutes a molecular language that allows the cell to communicate a specific outcome.

To understand how redox signalling pathways work, scientists on the EU-funded REDOXDYNAMICS study set out to investigate the temporal and qualitative dynamics of redox-based post-translational modifications in vivo. Since thioredoxins (TRXs) and glutaredoxins are implicated in these modifications, the project activities focused on these enzymes.

Using proteomics and mass spectrometry, researchers studied the redox proteome of Saccharomyces cerevisiae under diverse physiological growth conditions. Over 1 000 proteins were identified as TRX targets with roles in protein degradation, translation, redox homeostasis or stress responses. Interestingly, results suggest a further association of redox balance with autophagy, the process by which eukaryotic cells degrade intracellular material. The consortium successfully delineated the mechanism of redox regulation of one autophagy protein, providing invaluable insight into both processes.

Similar analysis in photosynthetic organisms such as Chlamydomonas reinhardtii indicated that redox regulation controls various fundamental processes, including carbon metabolism. Comparative analysis of the different proteomes regulated by glutathionylation, nitrosylation or TRX suggests that these modifications are interconnected.

The overall scope of REDOXDYNAMICS to elucidate the proteins and pathways subjected to redox control provided important information about the regulation of cell signalling. Given the role of cell signalling in health and disease, the study findings should impact both fundamental and biomedical research.