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Updated: Jan 6, 2026

Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
Published on: June 21, 2021
Reactive Sulfur Species and Protein Persulfidation: An Emerging Redox Axis in Human Health and Disease
Celia María Curieses Andrés1, Fernando Lobo2, José Manuel Pérez de la Lastra2
1Hospital Clínico Universitario de Valladolid, Avenida de Ramón y Cajal, 3, 47003 Valladolid, Spain.
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, p47phox) 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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