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A genome-wide and metabolic analysis determined the adaptive response of Arabidopsis cells to folate depletion induced by methotrexate.

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.

journal_name

Plant Physiol

journal_title

Plant physiology

authors

Loizeau K,De Brouwer V,Gambonnet B,Yu A,Renou JP,Van Der Straeten D,Lambert WE,Rébeillé F,Ravanel S

doi

10.1104/pp.108.130336

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

2083-95

issue

eissn

0032-0889

issn

1532-2548

pii

pp.108.130336

journal_volume

148

pub_type

杂志文章

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A genome-wide and metabolic analysis determined the adaptive response of Arabidopsis cells to folate depletion induced by methotrexate.