Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration.,Cell Metabolism

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Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration.
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-11-14 , DOI: 10.1016/j.cmet.2019.10.007
Jasmina Zivanovic ₁ , Emilia Kouroussis ₁ , Joshua B Kohl ₂ , Bikash Adhikari ₁ , Biljana Bursac ₁ , Sonia Schott-Roux ₁ , Dunja Petrovic ₁ , Jan Lj Miljkovic ₁ , Daniel Thomas-Lopez ₃ , Youngeun Jung ₄ , Marko Miler ₅ , Sarah Mitchell ₆ , Verica Milosevic ₅ , Jose Eduardo Gomes ₁ , Moran Benhar ₇ , Bruno Gonzalez-Zorn ₃ , Ivana Ivanovic-Burmazovic ₈ , Roberta Torregrossa ₉ , James R Mitchell ₆ , Matthew Whiteman ₉ , Guenter Schwarz ₂ , Solomon H Snyder ₁₀ , Bindu D Paul ₁₁ , Kate S Carroll ₄ , Milos R Filipovic ₁

Affiliation

CNRS, Institut de Biochimie et Génétique Cellulaires UMR5095, Université de Bordeaux, Bordeaux, France; Université de Bordeaux, CNRS, IBGC UMR5095, Bordeaux, France.
Department of Biochemistry, Center for Molecular Medicine, Institute of Biochemistry, University of Cologne, Cologne, Germany.
Departamento de Sanidad Animal, Facultad de Veterinaria and VISAVET, Universidad Complutense de Madrid, Madrid, Spain.
Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
Department of Cytology, Institute for Biological Research "Sinisa Stankovic", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Department of Biochemistry, Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.
Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
University of Exeter Medical School, St. Luke's Campus, Exeter, UK.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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.

中文翻译：

选择性过硫化物检测揭示了 S-硫酸化在进化上保守的抗衰老作用。

地球上的生命在很久以前就出现在富含硫化氢 (H2S) 的环境中，随之而来的是由 H2S 介导的蛋白质过硫化作为一种信号机制而进化。蛋白质过硫化（S-硫化）是反应性半胱氨酸残基的翻译后修饰，可调节蛋白质结构和/或功能。过硫化物由于其反应性以及与半胱氨酸的相似性而难以标记和研究。在这里，我们报告了一种使用基于双甲酮的探针进行化学选择性过硫化物生物共轭的简便策略，以在具有广泛用途的生物样品中实现高选择性、快速且稳定的过硫化物标记。使用这种方法，我们证明过硫化是一种进化上保守的修饰，细胞利用过硫化波来解决磺酰化并防止不可逆的半胱氨酸过度氧化，从而保留蛋白质功能。我们报告了与年龄相关的过硫化作用下降，这种下降在整个进化边界中都是保守的。因此，增加过硫化作用的饮食或药物干预与延长寿命和提高应对应激刺激的能力有关。

更新日期：2019-11-14

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