Ghent University Academic Bibliography

Advanced

A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate

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 (2008) PLANT PHYSIOLOGY. 148(4). p.2083-2095
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
S-ADENOSYLMETHIONINE, PURINE BIOSYNTHESIS, SACCHAROMYCES-CEREVISIAE, SUBCELLULAR-LOCALIZATION, GENE-EXPRESSION, ADENOSYL-L-METHIONINE, ONE-CARBON METABOLISM, P-AMINOBENZOATE BRANCH, PLANTS, PROTEIN
journal title
PLANT PHYSIOLOGY
Plant Physiol.
volume
148
issue
4
pages
2083 - 2095
publisher
AMER SOC PLANT BIOLOGISTS
place of publication
15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
Web of Science type
Article
Web of Science id
000261501500027
JCR category
PLANT SCIENCES
JCR impact factor
6.11 (2008)
JCR rank
12/155 (2008)
JCR quartile
1 (2008)
ISSN
0032-0889
DOI
10.1104/pp.108.130336
language
English
UGent publication?
yes
classification
A1
id
513273
handle
http://hdl.handle.net/1854/LU-513273
date created
2009-03-03 10:56:26
date last changed
2009-03-03 13:55:59
@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},
  keyword      = {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://dx.doi.org/10.1104/pp.108.130336},
  volume       = {148},
  year         = {2008},
}

Chicago
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.
APA
Loizeau, K., De Brouwer, V., Gambonnet, B., Yu, A., Renou, J.-P., Van Der Straeten, D., Lambert, W., et al. (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.
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. 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA: AMER SOC PLANT BIOLOGISTS; 2008;148(4):2083–95.
MLA
Loizeau, Karen, Veerle De Brouwer, Bernadette Gambonnet, et al. “A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate.” PLANT PHYSIOLOGY 148.4 (2008): 2083–2095. Print.