Glutathione at the Interface of Specialized Sulfur Metabolism and Sulfur Homeostasis

Abstract

Glutathione (GSH) is a central component of plant sulfur metabolism, best known for its roles in redox homeostasis, detoxification, and stress protection. Increasing evidence indicates that GSH also functions at the interface between primary and specialized sulfur metabolism. In plants, the best-characterized examples are concentrated in a limited number of lineages, particularly Brassicaceae and Allium species, where GSH is recruited into glucosinolate, camalexin, and S-alk(en)ylcysteine sulfoxide biosynthesis. Emerging observations further highlight the contribution of GSH degradation enzymes to sulfur transfer during specialized metabolite formation, linking GSH turnover to broader sulfur allocation networks. Beyond biosynthesis, GSH conjugation plays critical roles during specialized metabolite degradation by reducing the reactivity of intermediates, shaping immune-related metabolic outcomes, and enabling sulfur recycling through coordinated pathways of GSH degradation and resynthesis. Comparable GSH-dependent strategies in microbes and animals underscore the evolutionary conservation of GSH as a versatile metabolic scaffold. Collectively, these findings support a revised view in which specialized metabolism is embedded within dynamic GSH-dependent sulfur fluxes rather than functioning as an isolated sulfur sink. This review aims to integrate recent advances that highlight the role of GSH in connecting primary and specialized sulfur metabolism in response to environmental and developmental cues.