A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate
- Author
- Karen Loizeau, Veerle De Brouwer (UGent) , Bernadette Gambonnet, Agnes Yu, Jean-Pierre Renou, Dominique Van Der Straeten (UGent) , Willy Lambert (UGent) , Fabrice Rebeille and Stephane Ravanel
- Organization
- Abstract
- Control of folate homeostasis is essential to sustain the demand for one-carbon (C1) units that are necessary for major biological functions, including nucleotide synthesis and methylation reactions. In this study, we analyzed the genome-wide and metabolic adaptive response of Arabidopsis ( Arabidopsis thaliana) cells to folate depletion induced by the antifolate methotrexate. Drug treatment induced a response typical to xenobiotic stress and important changes in folate content and composition. This resulted in a reduction of cell division and primary energy metabolism that was likely associated with perturbation of nucleotide homeostasis. Through a modification of serine metabolism, folate depletion also induced O-acetylserine accumulation and mimicked sulfur deficiency response. The major adaptive response to folate limitation concerned the composition of the folate pool rather than the intracellular level of cofactors. Thus, no significant change in the expression of genes involved in cofactor synthesis, degradation, or trafficking was observed. However, changes in the distribution of C1 derivative pools and increased expression levels for transcripts coding enzymes manipulating C1 moieties in plastids suggested a reorientation of C1 units toward the synthesis of purine and thymidylate. Also, no genomic or metabolic adaptation was built up to counterbalance the major impairment of the methyl index, which controls the efficiency of methylation reactions in the cell. Together, these data suggested that the metabolic priority of Arabidopsis cells in response to folate limitation was to shuttle the available folate derivatives to the synthesis of nucleotides at the expense of methylation reactions.
- Keywords
- S-ADENOSYLMETHIONINE, PURINE BIOSYNTHESIS, SACCHAROMYCES-CEREVISIAE, SUBCELLULAR-LOCALIZATION, GENE-EXPRESSION, ADENOSYL-L-METHIONINE, ONE-CARBON METABOLISM, P-AMINOBENZOATE BRANCH, PLANTS, PROTEIN
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-513273
- MLA
- Loizeau, Karen, et al. “A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate.” PLANT PHYSIOLOGY, vol. 148, no. 4, AMER SOC PLANT BIOLOGISTS, 2008, pp. 2083–95, doi:10.1104/pp.108.130336.
- APA
- Loizeau, K., De Brouwer, V., Gambonnet, B., Yu, A., Renou, J.-P., Van Der Straeten, D., … Ravanel, S. (2008). A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate. PLANT PHYSIOLOGY, 148(4), 2083–2095. https://doi.org/10.1104/pp.108.130336
- Chicago author-date
- Loizeau, Karen, Veerle De Brouwer, Bernadette Gambonnet, Agnes Yu, Jean-Pierre Renou, Dominique Van Der Straeten, Willy Lambert, Fabrice Rebeille, and Stephane Ravanel. 2008. “A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate.” PLANT PHYSIOLOGY 148 (4): 2083–95. https://doi.org/10.1104/pp.108.130336.
- Chicago author-date (all authors)
- Loizeau, Karen, Veerle De Brouwer, Bernadette Gambonnet, Agnes Yu, Jean-Pierre Renou, Dominique Van Der Straeten, Willy Lambert, Fabrice Rebeille, and Stephane Ravanel. 2008. “A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate.” PLANT PHYSIOLOGY 148 (4): 2083–2095. doi:10.1104/pp.108.130336.
- Vancouver
- 1.Loizeau K, De Brouwer V, Gambonnet B, Yu A, Renou J-P, Van Der Straeten D, et al. A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate. PLANT PHYSIOLOGY. 2008;148(4):2083–95.
- IEEE
- [1]K. Loizeau et al., “A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate,” PLANT PHYSIOLOGY, vol. 148, no. 4, pp. 2083–2095, 2008.
@article{513273, abstract = {{Control of folate homeostasis is essential to sustain the demand for one-carbon (C1) units that are necessary for major biological functions, including nucleotide synthesis and methylation reactions. In this study, we analyzed the genome-wide and metabolic adaptive response of Arabidopsis ( Arabidopsis thaliana) cells to folate depletion induced by the antifolate methotrexate. Drug treatment induced a response typical to xenobiotic stress and important changes in folate content and composition. This resulted in a reduction of cell division and primary energy metabolism that was likely associated with perturbation of nucleotide homeostasis. Through a modification of serine metabolism, folate depletion also induced O-acetylserine accumulation and mimicked sulfur deficiency response. The major adaptive response to folate limitation concerned the composition of the folate pool rather than the intracellular level of cofactors. Thus, no significant change in the expression of genes involved in cofactor synthesis, degradation, or trafficking was observed. However, changes in the distribution of C1 derivative pools and increased expression levels for transcripts coding enzymes manipulating C1 moieties in plastids suggested a reorientation of C1 units toward the synthesis of purine and thymidylate. Also, no genomic or metabolic adaptation was built up to counterbalance the major impairment of the methyl index, which controls the efficiency of methylation reactions in the cell. Together, these data suggested that the metabolic priority of Arabidopsis cells in response to folate limitation was to shuttle the available folate derivatives to the synthesis of nucleotides at the expense of methylation reactions.}}, author = {{Loizeau, Karen and De Brouwer, Veerle and Gambonnet, Bernadette and Yu, Agnes and Renou, Jean-Pierre and Van Der Straeten, Dominique and Lambert, Willy and Rebeille, Fabrice and Ravanel, Stephane}}, issn = {{0032-0889}}, journal = {{PLANT PHYSIOLOGY}}, keywords = {{S-ADENOSYLMETHIONINE,PURINE BIOSYNTHESIS,SACCHAROMYCES-CEREVISIAE,SUBCELLULAR-LOCALIZATION,GENE-EXPRESSION,ADENOSYL-L-METHIONINE,ONE-CARBON METABOLISM,P-AMINOBENZOATE BRANCH,PLANTS,PROTEIN}}, language = {{eng}}, number = {{4}}, pages = {{2083--2095}}, publisher = {{AMER SOC PLANT BIOLOGISTS}}, title = {{A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate}}, url = {{http://doi.org/10.1104/pp.108.130336}}, volume = {{148}}, year = {{2008}}, }
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