Sulfur Partitioning between Glutathione and Protein Synthesis Determines Plant Growth1[OPEN]

Glutamate cysteine ligase activity determines flux of sulfur into protein synthesis via the Target of Rapamycin sensor kinase in Arabidopsis. Photoautotrophic organisms must efficiently allocate their resources between stress-response pathways and growth-promoting pathways to be successful in a constantly changing environment. In this study, we addressed the coordination of sulfur flux between the biosynthesis of the reactive oxygen species scavenger glutathione (GSH) and protein translation as one example of a central resource allocation switch. We crossed the Arabidopsis (Arabidopsis thaliana) GSH synthesis-depleted cadmium-sensitive cad2-1 mutant, which lacks glutamate cysteine (Cys) ligase, into the sulfite reductase sir1-1 mutant, which suffers from a significantly decreased flux of sulfur into Cys and, consequently, is retarded in growth. Surprisingly, depletion of GSH synthesis promoted the growth of the sir1-1 cad2-1 double mutant (s1c2) when compared with sir1-1. Determination of GSH levels and in vivo live-cell imaging of the reduction-oxidation-sensitive green fluorescent protein sensor demonstrated significant oxidation of the plastidic GSH redox potential in cad2-1 and s1c2. This oxidized GSH redox potential aligned with significant activation of plastid-localized sulfate reduction and a significantly higher flux of sulfur into proteins. The specific activation of the serine/threonine sensor kinase Target of Rapamycin (TOR) in cad2-1 and s1c2 was the trigger for reallocation of Cys from GSH biosynthesis into protein translation. Activation of TOR in s1c2 enhanced ribosome abundance and partially rescued the decreased meristematic activity observed in sir1-1 mutants. Therefore, we found that the coordination of sulfur flux between GSH biosynthesis and protein translation determines growth via the regulation of TOR.

[1]  Kazuki Saito,et al.  RETRACTED ARTICLE: Sulfur availability regulates plant growth via glucose-TOR signaling , 2017, Nature Communications.

[2]  J. Jez,et al.  Structural biology and regulation of the plant sulfation pathway. , 2016, Chemico-biological interactions.

[3]  Colin J. Jackson,et al.  Sensing and signaling of oxidative stress in chloroplasts by inactivation of the SAL1 phosphoadenosine phosphatase , 2016, Proceedings of the National Academy of Sciences.

[4]  M. Schmid,et al.  Integration of light and metabolic signals for stem cell activation at the shoot apical meristem , 2016, eLife.

[5]  Marten Moore,et al.  Redox Regulation of Cytosolic Translation in Plants. , 2016, Trends in plant science.

[6]  D. Largaespada,et al.  mTORC1 Coordinates Protein Synthesis and Immunoproteasome Formation via PRAS40 to Prevent Accumulation of Protein Stress. , 2016, Molecular cell.

[7]  C. Foyer,et al.  Low glutathione regulates gene expression and the redox potentials of the nucleus and cytosol in Arabidopsis thaliana. , 2015, Plant, cell & environment.

[8]  R. Hell,et al.  The role of compartment-specific cysteine synthesis for sulfur homeostasis during H2S exposure in Arabidopsis. , 2015, Plant & cell physiology.

[9]  Kazuki Saito,et al.  The significance of cysteine synthesis for acclimation to high light conditions , 2015, Front. Plant Sci..

[10]  B. Horváth,et al.  Balancing act: matching growth with environment by the TOR signalling pathway. , 2014, Journal of experimental botany.

[11]  H. Krishnan,et al.  Structure and Mechanism of Soybean ATP Sulfurylase and the Committed Step in Plant Sulfur Assimilation* , 2014, The Journal of Biological Chemistry.

[12]  A. Teleman,et al.  Regulation of TORC1 in Response to Amino Acid Starvation via Lysosomal Recruitment of TSC2 , 2014, Cell.

[13]  J. Sheen,et al.  The Role of Target of Rapamycin Signaling Networks in Plant Growth and Metabolism1 , 2014, Plant Physiology.

[14]  D. Verma,et al.  Ribosomal Protein S6, a Target of Rapamycin, Is Involved in the Regulation of rRNA Genes by Possible Epigenetic Changes in Arabidopsis * , 2013, The Journal of Biological Chemistry.

[15]  R. Hell,et al.  Successful Fertilization Requires the Presence of at Least One Major O-Acetylserine(thiol)lyase for Cysteine Synthesis in Pollen of Arabidopsis1[C][W][OPEN] , 2013, Plant Physiology.

[16]  E. Mancera-Martínez,et al.  TOR and S6K1 promote translation reinitiation of uORF‐containing mRNAs via phosphorylation of eIF3h , 2013, The EMBO journal.

[17]  J. Sheen,et al.  Glucose–TOR signalling reprograms the transcriptome and activates meristems , 2013, Nature.

[18]  Prakash Venglat,et al.  Target of Rapamycin Signaling Regulates Metabolism, Growth, and Life Span in Arabidopsis[W][OA] , 2012, Plant Cell.

[19]  R. Hell,et al.  Cysteine biosynthesis, in concert with a novel mechanism, contributes to sulfide detoxification in mitochondria of Arabidopsis thaliana. , 2012, The Biochemical journal.

[20]  C. Foyer,et al.  Glutathione in plants: an integrated overview. , 2012, Plant, cell & environment.

[21]  J. Jez,et al.  Structural basis and evolution of redox regulation in plant adenosine-5′-phosphosulfate kinase , 2011, Proceedings of the National Academy of Sciences.

[22]  Markus Wirtz,et al.  Evidence for a SAL1-PAP Chloroplast Retrograde Pathway That Functions in Drought and High Light Signaling in Arabidopsis[C][W][OA] , 2011, Plant Cell.

[23]  B. Poinssot,et al.  Glutathione Deficiency of the Arabidopsis Mutant pad2-1 Affects Oxidative Stress-Related Events, Defense Gene Expression, and the Hypersensitive Response1[C][W][OA] , 2011, Plant Physiology.

[24]  K. Inoki,et al.  Redox Regulates Mammalian Target of Rapamycin Complex 1 (mTORC1) Activity by Modulating the TSC1/TSC2-Rheb GTPase Pathway* , 2011, The Journal of Biological Chemistry.

[25]  Hideki Takahashi,et al.  Sulfur assimilation in photosynthetic organisms: molecular functions and regulations of transporters and assimilatory enzymes. , 2011, Annual review of plant biology.

[26]  C. Foyer,et al.  Ascorbate and Glutathione: The Heart of the Redox Hub1 , 2011, Plant Physiology.

[27]  V. Rybin,et al.  Structure and Function of the Hetero-oligomeric Cysteine Synthase Complex in Plants* , 2010, The Journal of Biological Chemistry.

[28]  M. Reichelt,et al.  Sulfite Reductase Defines a Newly Discovered Bottleneck for Assimilatory Sulfate Reduction and Is Essential for Growth and Development in Arabidopsis thaliana[C][W] , 2010, Plant Cell.

[29]  M. Fricker,et al.  The NADPH-dependent thioredoxin system constitutes a functional backup for cytosolic glutathione reductase in Arabidopsis , 2009, Proceedings of the National Academy of Sciences.

[30]  M. Reichelt,et al.  Disruption of Adenosine-5′-Phosphosulfate Kinase in Arabidopsis Reduces Levels of Sulfated Secondary Metabolites[W] , 2009, The Plant Cell Online.

[31]  M. Fricker,et al.  Confocal imaging of glutathione redox potential in living plant cells , 2008, Journal of microscopy.

[32]  M. Gutensohn,et al.  Analysis of the Arabidopsis O-Acetylserine(thiol)lyase Gene Family Demonstrates Compartment-Specific Differences in the Regulation of Cysteine Synthesis[W] , 2008, The Plant Cell Online.

[33]  Jean-Pierre Jacquot,et al.  Redox-sensitive GFP in Arabidopsis thaliana is a quantitative biosensor for the redox potential of the cellular glutathione redox buffer. , 2007, The Plant journal : for cell and molecular biology.

[34]  J. Jez,et al.  Thiol-Based Regulation of Redox-Active Glutamate-Cysteine Ligase from Arabidopsis thaliana , 2007, The Plant Cell Online.

[35]  J. Sheen,et al.  Arabidopsis mesophyll protoplasts: a versatile cell system for transient gene expression analysis , 2007, Nature Protocols.

[36]  O. Loudet,et al.  Natural variation for sulfate content in Arabidopsis thaliana is highly controlled by APR2 , 2007, Nature Genetics.

[37]  J. Gershenzon,et al.  Altered Glucosinolate Hydrolysis in Genetically Engineered Arabidopsis thaliana and its Influence on the Larval Development of Spodoptera littoralis , 2006, Journal of Chemical Ecology.

[38]  A. Wachter,et al.  Structural Basis for the Redox Control of Plant Glutamate Cysteine Ligase* , 2006, Journal of Biological Chemistry.

[39]  A. Wachter,et al.  Maturation of Arabidopsis Seeds Is Dependent on Glutathione Biosynthesis within the Embryo1[C] , 2006, Plant Physiology.

[40]  M. Hall,et al.  TOR Signaling in Growth and Metabolism , 2006, Cell.

[41]  D. Verma,et al.  Arabidopsis TARGET OF RAPAMYCIN Interacts with RAPTOR, Which Regulates the Activity of S6 Kinase in Response to Osmotic Stress Signals , 2005, The Plant Cell Online.

[42]  S. Grzesiek,et al.  The Solution Structure of the FATC Domain of the Protein Kinase Target of Rapamycin Suggests a Role for Redox-dependent Structural and Cellular Stability* , 2005, Journal of Biological Chemistry.

[43]  A. Wachter,et al.  Differential targeting of GSH1 and GSH2 is achieved by multiple transcription initiation: implications for the compartmentation of glutathione biosynthesis in the Brassicaceae. , 2004, The Plant journal : for cell and molecular biology.

[44]  R. Hell,et al.  Regulation of Sulfate Uptake and Expression of Sulfate Transporter Genes in Brassica oleracea as Affected by Atmospheric H2S and Pedospheric Sulfate Nutrition1 , 2004, Plant Physiology.

[45]  H. Rennenberg,et al.  Regulation of sulphate assimilation by glutathione in poplars (Populus tremula x P. alba) of wild type and overexpressing gamma-glutamylcysteine synthetase in the cytosol. , 2004, Journal of experimental botany.

[46]  T. Leustek,et al.  Regulation of the plant-type 5'-adenylyl sulfate reductase by oxidative stress. , 2001, Biochemistry.

[47]  D. Inzé,et al.  The ROOT MERISTEMLESS1/CADMIUM SENSITIVE2 Gene Defines a Glutathione-Dependent Pathway Involved in Initiation and Maintenance of Cell Division during Postembryonic Root Development , 2000, Plant Cell.

[48]  C. Cobbett,et al.  The glutathione-deficient, cadmium-sensitive mutant, cad2-1, of Arabidopsis thaliana is deficient in gamma-glutamylcysteine synthetase. , 1998, The Plant journal : for cell and molecular biology.

[49]  B. Touraine,et al.  Glutathione-Mediated Regulation of ATP Sulfurylase Activity, SO42- Uptake, and Oxidative Stress Response in Intact Canola Roots , 1997, Plant physiology.

[50]  R. Hell,et al.  λ-Glutamylcysteine synthetase in higher plants: catalytic properties and subcellular localization , 1990, Planta.

[51]  M. Reichelt,et al.  System analysis of metabolism and the transcriptome in Arabidopsis thaliana roots reveals differential co-regulation upon iron, sulfur and potassium deficiency. , 2017, Plant, cell & environment.

[52]  R. Hell,et al.  Sulfide detoxification in plant mitochondria. , 2015, Methods in enzymology.

[53]  B. Pogson,et al.  Balancing metabolites in drought: the sulfur assimilation conundrum. , 2013, Trends in plant science.

[54]  E. Mancera-Martínez,et al.  TOR and S 6 K 1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF 3 h , 2013 .