To efficiently control cellular processes, nature uses posttranslational modifications of proteins. Owning to unique sulfur chemistry, cysteine is the amino acid that could be subjected to the most diverse range of posttranslational modifications. One such modifications is caused by a gasotransmitter hydrogen sulfide (H2S), where an extra sulfur is added to cysteines forming persulfides. The pioneering work of our team in the past decade identified key mechanisms of biological chemistry of H2S, pointing out that protein persulfidation might represents the main way through which this gasotrasnmitter conveys its biological and pharmacological effects, particularly its anti-aging effects. Therefore, by combining the unique methodology for persulfide labelling developed in our group, with proteomics, metabolomics and classical biochemistry, and working on different model systems (cells, C. elegans, rodents) we intend to (i) gain high-resolution structural, functional, quantitative, and spatio-temporal information on persulfidation dynamics and position this evolutionary conserved posttranslational modification in the global cell signalling scheme, particularly in relation to other cysteine posttranslational modifications (ii) understand the intricate relation between aging and PSSH and (iii) identify the protein targets whose change of function by persulfidation is implicated in aging and disease progression. These studies are not only designed to provide contribution to the fundamental understanding of intracellular signalling, but to pave the way for the development of innovative therapeutic strategies that will permit targeted redox control of the cell metabolism and delay aging and disease progression.
