Download PDF
Plant Biol (Stuttg) 2007; 9(5): 565-572
DOI: 10.1055/s-2007-965580
Review Article

Georg Thieme Verlag Stuttgart KG · New York

Novel Insight into the Regulation of GSH Biosynthesis in Higher Plants

T. Rausch1 , R. Gromes1 , V. Liedschulte1 , I. Müller1 , J. Bogs1 , V. Galovic1 , 2 , A. Wachter1 , 3
  • 1Heidelberg Institute of Plant Sciences (HIP), University of Heidelberg, Im Neuenheimer Feld 360, 69120 Heidelberg, Germany
  • 2Institute of Field and Vegetable Crops, Small Grains Department, Maksima Gorkog 30, 21000 Novi Sad, Serbia and Montenegro
  • 3Yale University, Department of Molecular, Cellular and Developmental Biology, KBT 510, 266 Whitney Avenue, New Haven, CT 06511, USA
Further Information

Publication History

Received: May 7, 2007

Accepted: June 10, 2007

Publication Date:
13 September 2007 (online)

   Permissions and Reprints

Abstract

In higher plants, the redox-active tripeptide glutathione (GSH) fulfills a plethora of functions. These include its pivotal role for maintaining the cellular redox poise and its involvement in detoxification of heavy metals and xenobiotics. Intimately linked to these functions, GSH also acts as a cellular signal, mediating control of enzyme and/or regulatory protein activities, either directly or via glutaredoxins. The redox potential of the GSH/GSSG couple is not only affected by the GSH/GSSG ratio but also by changes in GSH synthesis and/or degradation. As this couple operates as redox buffer in several cellular compartments, the regulation of GSH biosynthesis and transport (both intra- and intercellularly) are fundamental to the maintenance of cellular redox homeostasis during plant development and, even more so, when plants are exposed to biotic or abiotic stress. This review highlights novel aspects of GSH biosynthesis and transport with a focus on the regulation of the GSH1 (= γ-glutamylcysteine synthetase) enzyme. Interestingly, GSH1 appears to be exclusively confined to the plastids, whereas the second biosynthetic enzyme, GSH2, is predominantly localized in the cytosol. GSH1 expression and enzyme activity are under multiple controls, extending from transcriptional regulation to post-translational redox control. Now that the plant GSH1 protein structure has been solved, the molecular basis of GSH1 function and redox regulation can be addressed. The review concludes with a discussion of the simultaneous changes observed for GSH synthesis, transport, and metabolism during Cd-induced phytochelatin accumulation.

Key words

Glutathione - γ-glutamylcysteine synthetase - compartmentation - redox control - GSH transporter - phytochelatin synthase.

References

  • 1 Alfenito M. R., Souer E., Goodman C. D., Buell R., Mol J., Koes R., Walbot V.. Functional complementation of anthocyanin sequestration in the vacuole by widely divergent glutathione S-transferases.  Plant Cell. (1998);  10 1135-1149
    PubMedGoogle Scholar
  • 2 Ball L., Accotto G., Bechtold U.. et al. . Evidence for a direct link between glutathione biosynthesis and stress defense gene expression in Arabidopsis.  Plant Cell. (2004);  16 2448-2462
    CrossrefPubMedGoogle Scholar
  • 3 Berkowitz O., Wirtz M., Wolf A., Kuhlmann J., Hell R.. Use of biomolecular interaction analysis to elucidate the regulatory mechanism of the cysteine synthase complex from Arabidopsis thaliana.  Journal of Biological Chemistry. (2002);  277 30629-30634
    CrossrefPubMedGoogle Scholar
  • 4 Bogs J., Bourbouloux A., Cagnac O., Wachter A., Rausch T., Delrot S.. Functional characterization and expression analysis of a glutathione transporter, BjGT1, from Brassica juncea: evidence for regulation by heavy metal exposure.  Plant, Cell and Environment. (2003);  26 1703-1711
    CrossrefPubMedGoogle Scholar
  • 5 Bourbouloux A., Shahi P., Chakladar A., Delrot S., Bachhawat A. K.. Hgt1p, a high affinity glutathione transporter from the yeast Saccharomyces cerevisiae.  Journal of Biological Chemistry. (2000);  275 13259-13265
    CrossrefPubMedGoogle Scholar
  • 6 Cairns N. G., Pasternak M., Wachter A., Cobbett C. S., Meyer A. J.. Maturation of Arabidopsis seeds is dependent on glutathione biosynthesis within the embryo.  Plant Physiology. (2006);  141 446-455
    CrossrefPubMedGoogle Scholar
  • 7 Chen Z., Todd E., Young J.-L., Chang S.-C., Gallie D.. Increasing vitamin C content of plants through enhanced ascorbate recycling.  Proceedings of the National Academy of Sciences of the USA. (2003);  100 3525-3530
    CrossrefPubMedGoogle Scholar
  • 8 Chew O., Whelan J., Millar A. H.. Molecular definition of the ascorbate-glutathione cycle in Arabidopsis mitochondria reveals dual-targeting of antioxidant defenses in plants.  Journal of Biological Chemistry. (2003);  278 46869-46877
    CrossrefPubMedGoogle Scholar
  • 9 Clemens S., Palmgren M. G., Kramer U.. A long way ahead: understanding and engineering plant metal accumulation.  Trends in Plant Science. (2002);  7 309-315
    CrossrefPubMedGoogle Scholar
  • 10 Cobbett C., Goldsbrough P.. Phytochelatins and metallothioneins: roles in heavy metal detoxification and homeostasis.  Annual Review of Plant Biology. (2002);  53 159-182
    CrossrefPubMedGoogle Scholar
  • 11 Cobbett C. S., May M. J., Howden R., Rolls B.. The glutathione-deficient, cadmium-sensitive mutant, cad2-1, of Arabidopsis thaliana is deficient in γ-glutamylcysteine synthetase.  The Plant Journal. (1998);  16 73-78
    CrossrefPubMedGoogle Scholar
  • 12 Copley S. D., Dhillon J. K.. Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes.  Genome Biology. (2002);  3 1-16
    PubMedGoogle Scholar
  • 13 Creissen G., Reynolds H., Xue Y., Mullineaux P.. Simultaneous targeting of pea gluathione reductase and of a bacterial fusion protein to chloroplast and mitochondria in transgenic tobacco.  The Plant Journal. (1995);  8 167-175
    CrossrefPubMedGoogle Scholar
  • 14 Dong X. N.. NPR1, all things considered.  Current Opinion in Plant Biology. (2004);  7 547-552
    CrossrefPubMedGoogle Scholar
  • 15 Edwards R., Dixon D.. Plant glutathione transferases.  Methods in Enzymology. (2005);  401 169-186
    PubMedGoogle Scholar
  • 16 Edwards R., Dixon D. P., Walbot V.. Plant glutathione S-transferases: enzymes with multiple functions in sickness and in health.  Trends in Plant Science. (2000);  5 193-198
    CrossrefPubMedGoogle Scholar
  • 17 Foyer C., Noctor G.. Redox homeostasis and antioxidant signaling: a metabolic interface between stress perception and physiological responses.  Plant Cell. (2005);  17 1866-1875
    CrossrefPubMedGoogle Scholar
  • 18 Grill E., Winnacker E. L., Zenk M. H.. Phytochelatins, a class of heavy-metal binding polypeptides from plants, are functionally homologous to metallothioneins.  Proceedings of the National Academy of Sciences of the USA. (1987);  84 439-443
    PubMedGoogle Scholar
  • 19 Ha S. B., Smith A. P., Howden R., Dietrich W. M., Bugg S., O'Connell M. J., Goldsbrough P. B., Cobbett C. S.. Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe.  Plant Cell. (1999);  11 1153-1164
    CrossrefPubMedGoogle Scholar
  • 20 Haag-Kerwer A., Schäfer H. J., Heiss S., Walter C., Rausch T.. Cadmium exposure in Brassica juncea causes a decline in transpiration rate and leaf expansion without effect on photosynthesis.  Journal of Experimental Botany. (1999);  50 1827-1835
    CrossrefPubMedGoogle Scholar
  • 21 Hartmann T. N., Fricker M. D., Rennenberg H., Meyer A. J.. Cell-specific measurement of cytosolic glutathione in poplar leaves.  Plant, Cell and Environment. (2003);  26 965-975
    CrossrefPubMedGoogle Scholar
  • 22 Heiss S., Schäfer H. J., Haag-Kerwer A., Rausch T.. Cloning sulfur assimilation genes of Brassica juncea L. Cadmium differentially affects the expression of a putative low affinity sulfate transporter and isoforms of ATP sulfurylase and APS reductase.  Plant Molecular Biology. (1999);  39 847-857
    CrossrefPubMedGoogle Scholar
  • 23 Heiss S., Wachter A., Bogs J., Cobbett C., Rausch T.. Phytochelatin synthase (PCS) protein is induced in Brassica juncea leaves after prolonged Cd exposure.  Journal of Experimental Botany. (2003);  54 1-7
    CrossrefPubMedGoogle Scholar
  • 24 Hell R., Bergmann L.. γ-Glutamylcysteine synthetase in higher plants: catalytic properties and subcellular localization.  Planta. (1990);  180 603-612
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Hibi T., Nii H., Nakatsu T., Kimura A., Kato H., Hiratake J., Oda J.. Crystal structure of γ-glutamylcysteine synthetase: insights into the mechanism of catalysis by a key enzyme for glutathione homeostasis.  Proceedings of the National Academy of Sciences of the USA. (2004);  101 15052-15057
    CrossrefPubMedGoogle Scholar
  • 26 Horemans N., Foyer C. H., Asard H.. Transport and action of ascorbate at the plant plasma membrane.  Trends in Plant Science. (2000);  5 263-267
    CrossrefPubMedGoogle Scholar
  • 27 Hothorn M., Wachter A., Gromes R., Stuwe T., Rausch T., Scheffzek K.. Structural basis for the redox-control of plant glutamate cysteine ligase.  Journal of Biological Chemistry. (2006);  281 27557-27565
    CrossrefPubMedGoogle Scholar
  • 28 Jez J. M., Cahoon R. E., Bonnere E. R., Chen S.. Redox-regulation of glutathione synthesis in plants.  FASEB Journal. (2006);  20 A41-A42
    PubMedGoogle Scholar
  • 29 Jez J. M., Cahoon R. E., Chen S.. Arabidopsis thaliana glutamate-cysteine ligase. Functional properties, kinetic mechanism, and regulation of activity.  Journal of Biological Chemistry. (2004);  279 33463-33470
    CrossrefPubMedGoogle Scholar
  • 30 Jiménez A., Hernández J., Pastori G., del Rio L., Sevilla F.. Role of the ascorbate-glutathione cycle of mitochondria and peroxisomes in the senescence of pea leaves.  Plant Physiology,. (1998);  118 1327-1335
    CrossrefPubMedGoogle Scholar
  • 31 Kanwischer M., Porfirova S., Bergmuller E., Dormann P.. Alterations in tocopherol cyclase activity in transgenic and mutant plants of Arabidopsis affect tocopherol content, tocopherol composition, and oxidative stress.  Plant Physiology. (2005);  137 713-723
    CrossrefPubMedGoogle Scholar
  • 79 Klein M., Burla B., Martinoia E.. The multidrug resistance-associated proteins (MRP/ABCC) subfamily of ATP-binding cassette transporters in plants.  FEBS Letters. (2006);  580 1112-1122
    CrossrefPubMedGoogle Scholar
  • 32 Koh S., Wiles A. M., Sharp J. S., Naider F. R., Becker J. M., Stacey G.. An oligopeptide transporter gene family in Arabidopsis.  Plant Physiology. (2002);  128 21-29
    CrossrefPubMedGoogle Scholar
  • 33 Kuzniak E., Sklodowska M.. Compartment-specific role of the ascorbate-glutathione cycle in the response of tomato leaf cells to Botrytis cinerea infection.  Journal of Experimental Botany. (2005);  56 921-933
    CrossrefPubMedGoogle Scholar
  • 34 Leterrier M., Corpas F. J., Barroso J. B., Sandalio L. M., del Rio L. A.. Peroxisomal monodehydroascorbate reductase. Genomic clone characterization and functional analysis under environmental stress conditions.  Plant Physiology. (2005);  138 2111-2123
    CrossrefPubMedGoogle Scholar
  • 35 Leustek T., Saito K.. Sulfate transport and assimilation in plants.  Plant Physiology. (1999);  120 637-644
    CrossrefPubMedGoogle Scholar
  • 36 Lopez-Juez E.. Plastid biogenesis, between light and shadows.  Journal of Experimental Botany,. (2007);  58 11-26
    PubMedGoogle Scholar
  • 37 Marrs K. A.. The functions and regulation of glutathione S-transferases in plants.  Annual Review of Plant Physiology and Plant Molecular Biology. (1996);  47 127-158
    CrossrefPubMedGoogle Scholar
  • 38 May M. J., Leaver C. J.. Arabidopsis thaliana γ-glutamylcysteine synthetase is structurally unrelated to mammalian, yeast and E. coli homologs.  Proceedings of the National Academy of Sciences of the USA. (1994);  91 10059-10063
    CrossrefPubMedGoogle Scholar
  • 39 May M. J., Vernoux T., Sanchez-Fernandez R., Van Montagu M., Inzé D.. Evidence for posttranscriptional activation of γ-glutamylcysteine synthetase during plant stress responses.  Proceedings of the National Academy of Sciences of the USA. (1998);  95 12049-12054
    CrossrefPubMedGoogle Scholar
  • 40 Meyer A., May M. J., Fricker M.. Quantitative in vivo measurement of glutathione in Arabidopsis cells.  The Plant Journal. (2001);  27 67-78
    CrossrefPubMedGoogle Scholar
  • 41 Meyer A. J., Fricker M. D.. Control of demand-driven biosynthesis of glutathione in green Arabidopsis suspension culture cells.  Plant Physiology. (2002);  130 1927-1937
    CrossrefPubMedGoogle Scholar
  • 42 Meyer A. J., Hell R.. Glutathione homeostasis and redox-regulation by sulfhydryl groups.  Photosynthesis Research. (2005);  86 435-457
    PubMedGoogle Scholar
  • 43 Moran J. F., Iturbe-Ormaetxe I., Matamoros M. A., Rubio M. C., Clemente M. R., Brewin N. J., Becana M.. Glutathione and homoglutathione synthetases of legume nodules. Cloning, expression, and subcellular localization.  Plant Physiology. (2000);  124 1381-1392
    CrossrefPubMedGoogle Scholar
  • 44 Mou Z., Fan W., Dong X.. Inducers of plant systemic acquired resistance regulate NPR1 function through redox changes.  Cell. (2003);  113 935-944
    CrossrefPubMedGoogle Scholar
  • 45 Mullineaux P., Rausch T.. Glutathione, photosynthesis and the redox regulation of stress-responsive gene expression.  Photosynthesis Research. (2005);  86 459-474
    PubMedGoogle Scholar
  • 47 Nocito F. F., Lancilli C., Crema B., Fourcroy P., Davidian J.-C., Sacchi G. A.. Heavy metal stress and sulfate uptake in maize roots.  Plant Physiology. (2006);  141 1138-1148
    CrossrefPubMedGoogle Scholar
  • 48 Noctor G.. Metabolic signaling in defense and stress: the central roles of soluble redox couples.  Plant, Cell and Environment. (2006);  29 409-425
    CrossrefPubMedGoogle Scholar
  • 49 Noctor G., Gomez L., Vanacker H., Foyer C. H.. Interactions between biosynthesis, compartmentation and transport in the control of glutathione homeostasis and signalling.  Journal of Experimental Botany. (2002);  53 1283-1304
    CrossrefPubMedGoogle Scholar
  • 50 Ohkama-Ohtsu N., Radwan S., Peterson A., Zhao P., Badr A. F., Xiang C., Oliver J. J.. Characterization of the extracellular γ-glutamyl transpeptidases, GGT1 and GGT2, in Arabidopsis.  The Plant Journal. (2007);  49 865-877
    CrossrefPubMedGoogle Scholar
  • 51 Ortiz D. F., Ruscitti T., McCue K. F., Ow D. W.. Transport of metal-binding peptides by HMT1, a fission yeast ABC-type vacuolar membrane protein.  Journal of Biological Chemistry. (1995);  270 4721-4728
    CrossrefPubMedGoogle Scholar
  • 52 Palma J. M., Jimenez A., Sandalio L. M., Corpas F. J., Lundqvist M., Gomez M., Sevilla F. G., del Rio L. A.. Antioxidative enzymes from chloroplasts, mitochondria, and peroxisomes during leaf senescence of nodulated pea plants.  Journal of Experimental Botany. (2006);  57 1747-1758
    CrossrefPubMedGoogle Scholar
  • 53 Parisy V., Poinssot B., Owsianowski L., Buchala A., Glazebrook J., Mauch F.. Identification of PAD2 as γ-glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis.  The Plant Journal. (2007);  49 159-172
    CrossrefPubMedGoogle Scholar
  • 54 Pignocchi C., Foyer C. H.. Apoplastic ascorbate metabolism and its role in the regulation of cell signaling.  Current Opinion Plant Biology. (2003);  6 379-389
    CrossrefPubMedGoogle Scholar
  • 55 Pignocchi C., Kiddle G., Hernandez I., Foster S. J., Asensi A., Taybi T., Barnes J., Foyer C. H.. Ascorbate oxidase-dependent changes in the redox state of the apoplast modulate gene transcript accumulation leading to modified hormone signaling and orchestration of defense processes in tobacco.  Plant Physiology. (2006);  141 423-435
    CrossrefPubMedGoogle Scholar
  • 56 Rausch T., Wachter A.. Sulfur metabolism: a versatile platform for launching defence operations.  Trends in Plant Science. (2005);  10 503-509
    CrossrefPubMedGoogle Scholar
  • 57 Rouhier N., Villarejo A., Srivastava M., Gelhaye E., Keech O., Droux M., Finkemeier I., Samuelsson G., Dietz K., Jacquot J., Wingsle G.. Identification of plant glutaredoxin targets.  Antioxidant Redox Signal. (2005);  7 919-929
    PubMedGoogle Scholar
  • 58 Ruegsegger A., Brunold C.. Localization of γ-glutamylcysteine synthetase and glutathione synthetase activity in maize seedlings.  Plant Physiology. (1993);  101 561-566
    PubMedGoogle Scholar
  • 59 Saito K.. Sulfur assimilatory metabolism. The long and smelling road.  Plant Physiology. (2004);  136 2443-2450
    CrossrefPubMedGoogle Scholar
  • 60 Salt D. E., Rauser W. E.. MgATP-dependent transport of phytochelatins across the tonoplast of oat roots.  Plant Physiology. (1995);  107 1293-1301
    PubMedGoogle Scholar
  • 61 Sanmartin M., Drogoudi P. D., Lyons T., Barnes J., Kanellis A. K.. Over-expression of ascorbate oxidase in the apoplast of transgenic tobacco results in altered ascorbate and glutathione redox states and increased sensitivity to ozone.  Planta. (2003);  216 918-928
    PubMedGoogle Scholar
  • 62 Schäfer H. J., Haag-Kerwer A., Rausch T.. cDNA cloning and expression analysis of genes encoding GSH synthesis in roots of the heavy-metal accumulator Brassica juncea L. evidence for Cd induction of a putative mitochondrial γ-glutamylcysteine synthetase isoform.  Plant Molecular Biolology. (1998);  37 87-97
    PubMedGoogle Scholar
  • 63 Schröder P., Stampfl A.. Visualization of glutathione conjugation and inducibility of glutathione S-transferases in onion (Allium cepa L.) epidermal tissue.  Zeitschrift für Naturforschung Section C. (1999);  54 1033-1041
    PubMedGoogle Scholar
  • 64 Smith M. D.. Protein import into chloroplasts: an ever-evolving story.  Canadian Journal of Botany. (2006);  84 531-542
    CrossrefPubMedGoogle Scholar
  • 65 Storozhenko S., Belles-Boix E., Babiychuk E., Herouart D., Davey M. W., Slooten L., Van Montagu M., Inzé D., Kushnir S.. γ-Glutamyl transpeptidase in transgenic tobacco plants. Cellular localization, processing, and biochemical properties.  Plant Physiology. (2002);  128 1109-1119
    CrossrefPubMedGoogle Scholar
  • 66 The Arabidopsis Genome Initiative . Analysis of the genome sequence of the flowering plant Arabidopsis thaliana.  Nature. (2000);  408 796-815
    CrossrefPubMedGoogle Scholar
  • 67 Thomine S., Wang R., Ward J. M., Crawford N. M., Schroeder J. S.. Cadmium and iron transport by members of plant metal transporter family in Arabidopsis with homology to Nramp genes.  Proceedings of the National Academy of Sciences of the USA. (2000);  97 4991-4996
    CrossrefPubMedGoogle Scholar
  • 68 Vatamaniuk O. K., Mari S., Lu Y. P., Rea P. A.. Mechanism of heavy metal ion activation of phytochelatin (PC) synthase.  Journal of Biological Chemistry. (2000);  275 31451-31459
    CrossrefPubMedGoogle Scholar
  • 69 Vernoux T., Wilson R. C., Seeley  et al. K. A.. The ROOT MERISTEMLESS1/CADMIUM SENSITIVE2 gene defines a glutathione-dependent pathway involved in initiation and maintenance of cell division during postembryonic root development.  Plant Cell. (2000);  12 97-110
    CrossrefPubMedGoogle Scholar
  • 70 Wachter A.. Glutathion-Synthese und ‐Kompartimentierung in der Pflanze: Nachweis komplexer Regulationsmechanismen. Dissertation, Heidelberg University. (2004)
    Google Scholar
  • 71 Wachter A., Rausch T.. Regulation of glutathione (GSH) synthesis in plants: novel insight from Arabidopsis.  FAL Agricultural Research. (2005);  283 149-155
    PubMedGoogle Scholar
  • 72 Wachter A., Wolf S., Steininger H., Bogs J., Rausch T.. Differential targeting of GSH1 and GSH2 is achieved by multiple transcription initiation: implications for the compartmentation of glutathione biosynthesis in the Brassicaceaee.  The Plant Journal. (2005);  41 15-30
    CrossrefPubMedGoogle Scholar
  • 73 Xiang C., Bertrand D.. Glutathione synthesis in Arabidopsis: multilevel controls coordinate responses to stress. Brunold, C., Rennerberg, H., Dekok, L. J., Stulen, I., and Davidian, J. C., eds. Sulfur Nutrition and Sulfur Assimilation in Higher Plants. Bern; Paul Haupt (2000): 409-412
    Google Scholar
  • 74 Xiang C., Oliver D. J.. Glutathione metabolic genes coordinately respond to heavy metals and jasmonic acid in Arabidopsis.  Plant Cell. (1998);  10 1539-1550
    PubMedGoogle Scholar
  • 75 Xiang C., Werner B. L., Christensen E. M., Oliver D. J.. The biological functions of glutathione revisited in Arabidopsis transgenic plants with altered glutathione levels.  Plant Physiology. (2001);  126 564-574
    CrossrefPubMedGoogle Scholar
  • 76 Xing S., Lauri A., Zachgo S.. Redox regulation and flower development: a novel function for glutaredoxins.  Plant Biology. (2006);  8 547-555
    Article in Thieme ConnectPubMedGoogle Scholar
  • 77 Yazaki K.. ABC transporters involved in the transport of plant secondary metabolites.  FEBS Letters. (2006);  580 1183-1191
    CrossrefPubMedGoogle Scholar
  • 78 Zhang M. Y., Bourbouloux A., Cagnac O., Srikanth C. V., Rentsch D., Bachhawat A. K., Delrot S.. A novel family of transporters mediating the transport of glutathione derivatives in plants.  Plant Physiology. (2004);  134 482-491
    CrossrefPubMedGoogle Scholar

T. Rausch

Heidelberg Institute of Plant Sciences (HIP)
University of Heidelberg

Im Neuenheimer Feld 360

69120 Heidelberg

Germany

Email: trausch@hip.uni-hd.de

Editor: H. Rennenberg

      >