Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration

• DOI: 10.1016/j.cmet.2019.10.007
• Publication Date: 2019-11-14T15:40:55Z
• Authors: Jasmina Zivanovic; Emilia Kouroussis; Joshua B. Kohl; Bikash Adhikari; Biljana Bursac; Sonia Schott-Roux; Dunja Petrovic; Jan Lj. Miljkovic; Daniel Thomas-Lopez; Youngeun Jung; Marko Miler; Sarah Mitchell; Verica Milosevic; Jose Eduardo Gomes; Moran Benhar; Bruno Gonzalez-Zorn; Ivana Ivanovic-Bu...; Roberta Torregrossa; James R. Mitchell; Matthew Whiteman; Guenter Schwarz; Solomon H. Snyder; Bindu D. Paul; Kate S. Carroll; Milos R. Filipovic
• Keywords: Sulfenylation; Male; sulfenylation; Aging; Redox signaling; [SDV]Life Sciences [q-bio]; hydrogen sulfide; 610; hydrogen peroxide; Saccharomyces cerevisiae; Protein persulfidation; Cell Line; Mice; Escherichia coli; Animals; Humans; Cysteine; Hydrogen Sulfide; Rats, Wistar; redox signaling; Caenorhabditis elegans; Sulfonylation; Calorie restriction; sulfonylation; Hydrogen sulfide; Staining and Labeling; protein persulfidation; Cyclohexanones; aging; calorie restriction; Fibroblasts; Hydrogen peroxide; Rats; Mice, Inbred C57BL; Oxidative Stress; Drosophila melanogaster; Protein Processing, Post-Translational; sulfinylation; Sulfinylation

Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli.