Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration
Cell metabolism publish this investigation article
December 3rd, 2019
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
Zivanovic J., Kouroussis E., Kohl JB., Adhikari B., Bursac B., Schott-Roux S., Petrovic D., Miljkovic JL., Thomas-Lopez D., Jung Y., Miler M., Mitchell S., Milosevic V., Gomes JE., Benhar M., Gonzalez-Zorn B., Ivanovic-Burmazovic I., Torregrossa R., Mitchell JR., Whiteman M., Schwarz G., Snyder SH., Paul BD., Carroll KS. and Filipovic MR.
 | Institut de Biochimie et Génétique Cellulaires. Université de Bordeaux. |
 | Centre National de la Recherche Scientifique (CNRS). |
 | Center for Molecular Medicine. Institute of Biochemistry. University of Cologne. |
 | Servicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM). |
| Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
 | Department of Chemistry. The Scripps Research Institute. |
 | Institute for Biological Research Sinisa Stankovic. National Institute of Republic of Serbia. University of Belgrade. |
 | Department of Genetics and Complex Diseases. Harvard School of Public Health. |
 | Rappaport Institute for Research in the Medical Sciences. Faculty of Medicine. Technion - Israel Institute of Technology. |
 | Department of Chemistry and Pharmacy. Friedrich-Alexander-Universität Erlangen-Nürnberg. |
 | Medical School. University of Exeter. |
 | The Solomon H. Snyder Department of Neuroscience. Johns Hopkins University School of Medicine. |
| Department of Pharmacology and Molecular Sciences. Johns Hopkins University School of Medicine. |
| Department of Psychiatry. Johns Hopkins University School of Medicine. |
