Reactive Sulfur Species and Protein Persulfidation: An Emerging Redox Axis in Human Health and Disease.

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Issues in Molecular Biology Pub Date : 2025-09-16 DOI:10.3390/cimb47090765

Celia María Curieses Andrés, Fernando Lobo, José Manuel Pérez de la Lastra, Elena Bustamante Munguira, Celia Andrés Juan, Eduardo Pérez Lebeña

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Abstract

Reactive sulfur species (RSS)-hydrogen sulfide (H₂S), low-molecular-weight persulfides/polysulfides and protein persulfidation-constitute a third redox axis alongside ROS and RNS. Nanomolar H₂S, produced by trans-sulfuration (CBS/CSE) and 3-MST, is oxidized by sulfide-quinone reductase to persulfides that fuel the respiratory chain while curbing superoxide. Reversible persulfidation reprograms cysteine sensors in metabolism (GAPDH), inflammation (NLRP3, p47^phox) and transcription (Keap1/NRF2), linking RSS to energy balance, vasodilation, innate immunity and neuroplasticity. Disrupted sulfur signaling-deficit or overload-contributes to heart failure, sarcopenia, neurodegeneration, cancer and post-COVID syndromes. Therapeutically, slow-release donors (SG1002, GYY4137), mitochondria-targeted vectors (AP39), photo- or thiol-activated "smart" scaffolds, diet-derived polysulfides/isothiocyanates and microbiota engineering aim to restore the protective RSS window. Key challenges are a narrow therapeutic margin and real-time quantification of persulfide fluxes. Harnessing RSS therefore offers a route to rebalance redox homeostasis across diverse chronic diseases.

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活性硫和蛋白质过硫化：人类健康和疾病中一个新兴的氧化还原轴。

活性硫物质（RSS）——硫化氢（H2S）、低分子量过硫化物/多硫化物和蛋白质过硫化物——与ROS和RNS一起构成了第三条氧化还原轴。由反式硫化（CBS/CSE）和3-MST产生的纳摩尔H2S被硫化物-醌还原酶氧化成过硫化物，为呼吸链提供燃料，同时抑制超氧化物。可逆过硫化重编程代谢（GAPDH）、炎症（NLRP3、p47phox）和转录（Keap1/NRF2）中的半胱氨酸传感器，将RSS与能量平衡、血管舒张、先天免疫和神经可塑性联系起来。硫信号缺失或超载会导致心力衰竭、肌肉减少症、神经退行性疾病、癌症和covid - 19后综合征。在治疗方面，缓释供体（SG1002, GYY4137），线粒体靶向载体（AP39），光或硫醇激活的“智能”支架，饮食来源的多硫化物/异硫氰酸酯和微生物群工程旨在恢复保护性RSS窗口。关键的挑战是狭窄的治疗范围和过硫通量的实时量化。因此，利用RSS提供了一种途径来重新平衡各种慢性疾病的氧化还原稳态。

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来源期刊

Current Issues in Molecular Biology 生物-生化研究方法

CiteScore

2.90

自引率

3.20%

发文量

380

审稿时长

>12 weeks

期刊介绍： Current Issues in Molecular Biology (CIMB) is a peer-reviewed journal publishing review articles and minireviews in all areas of molecular biology and microbiology. Submitted articles are subject to an Article Processing Charge (APC) and are open access immediately upon publication. All manuscripts undergo a peer-review process.