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

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• Protein persulfidation (S-sulfhydration) is a post-translational modification involving hydrogen sulfide (H2S).
• It regulates protein function but is challenging to study due to persulfide reactivity.
• This modification is ancient, originating in Earth's early H2S-rich environment.

Purpose of the Study:

• To develop a facile and chemoselective method for labeling persulfides in biological samples.
• To investigate the role of protein persulfidation in cellular processes and its evolutionary conservation.
• To explore the relationship between persulfidation, aging, and longevity.

Main Methods:

• Development of dimedone-based probes for chemoselective persulfide bioconjugation.
• Application of the probes for rapid and robust persulfide labeling in biological systems.
• Comparative analysis of persulfidation levels across different species and ages.

Main Results:

• A novel strategy for selective persulfide labeling was established using dimedone-based probes.
• Protein persulfidation was confirmed as an evolutionarily conserved modification.
• Cells utilize waves of persulfidation to manage cysteine oxidation and preserve protein function.
• An age-associated decline in protein persulfidation was observed across species.
• Interventions increasing persulfidation correlated with enhanced longevity and stress resistance.

Conclusions:

• The developed method enables robust study of protein persulfidation.
• Persulfidation plays a critical role in cellular redox homeostasis and protein function.
• Age-related decline in persulfidation impacts healthspan, suggesting therapeutic potential.