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Multilevel Regulation of Glutathione Homeostasis in
Higher Plants
Chengbin Xiang and David J. Oliver
Iowa State University, Ames, Iowa
539I. INTRODUCTION
Glutathione (GSH), the tripeptide -glutamylcysteinyl glycine, is ubiquitous and the most abundant non-
protein thiol in plant cells [1]. The unique structure of GSH gives this molecule the exceptional stability,
high water solubility, and redox properties that make GSH well suited to perform diverse functions. GSH
is proposed to play important roles in defense. These include scavenging reactive oxygen species (ROS)
through the ascorbate-GSH cycle [2–5], detoxifying a variety of organic electrophilic contaminants
through glutathione S-transferases [6] and heavy metals through the phytochelatins (PCs) synthesized by
PC synthase [7–9] upon heavy metal exposure [10,11]. In addition, GSH is important in organic sulfur
storage, transport, and metabolism [12].
GSH is enzymatically synthesized from glutamate, cysteine, and glycine by two ATP-dependent re-
action [13]. The first reaction is rate limiting and forms -glutamylcysteine ( -EC) from glutamate and cys-
teine by the enzyme -EC synthetase ( -ECS) [14], which is encoded by GSH1[15]. GSH is then synthe-
sized by the ligation of -EC and glycine in the reaction catalyzed by the enzyme GSH synthetase encoded
byGSH2[16]. The end product, GSH, is believed to feedback inhibit the rate-limiting enzyme, -ECS, so
that a steady-state cellular GSH level is metabolically controlled. When GSH is oxidized as part of its an-
tioxidant activity, it forms GSH disulfide (GSSG) and constitutes a major cellular redox buffer. GSSG, the
oxidized form of GSH, is reduced back to GSH with reducing equivalents from reduced nicotinamide-ade-
nine dinucleotide phosphate (NADPH) by GSH reductases that are encoded by GR1andGR2[17].
Because of the diverse functions of GSH in plants, it is not surprising that its synthesis is controlled
by a network of complex regulatory mechanisms. This multilevel regulation provides the ability for GSH
synthesis to respond to all the different environmental stress factors that GSH must mitigate. These com-
plex regulatory mechanisms are starting to be uncovered. This review chapter focuses on the regulation
of GSH synthesis in response to environmental stress. A working model is presented to depict the com-
plexity of GSH homeostasis and autoregulation of GSH synthesis. GSH transport and turnover, which
contribute to GSH homeostasis in the whole plant body, are also discussed.
II. REGULATION OF GSH HOMEOSTASIS
GSH homeostasis in the whole plant body is dynamically established through a concerted interplay of
synthesis, transport, utilization, and degradation. Little is known about the regulation of these processes.