title: Regulation of one-carbon metabolism in Arabidopsis: the N-terminal regulatory domain of cystathionine gamma-synthase is cleaved in response to folate starvation.
abstract: In all organisms, control of folate homeostasis is of vital importance to sustain the demand for one-carbon (C1) units that are essential in major metabolic pathways. In this study we induced folate deficiency in Arabidopsis (Arabidopsis thaliana) cells by using two antifolate inhibitors. This treatment triggered a rapid and important decrease in the pool of folates with significant modification in the distribution of C1-substituted folate coenzymes, suggesting an adaptive response to favor a preferential shuttling of the flux of C1 units to the synthesis of nucleotides over the synthesis of methionine (Met). Metabolic profiling of folate-deficient cells indicated important perturbation of the activated methyl cycle because of the impairment of Met synthases that are deprived of their substrate 5-methyl-tetrahydrofolate. Intriguingly, S-adenosyl-Met and Met pools declined during the initial period of folate starvation but were further restored to typical levels. Reestablishment of Met and S-adenosyl-Met homeostasis was concomitant with a previously unknown posttranslational modification that consists in the removal of 92 amino acids at the N terminus of cystathionine gamma-synthase (CGS), the first specific enzyme for Met synthesis. Rescue experiments and analysis of different stresses indicated that CGS processing is specifically associated with perturbation of the folates pool. Also, CGS processing involves chloroplastic serine-type proteases that are expressed in various plant species subjected to folate starvation. We suggest that a metabolic effector, to date unidentified, can modulate CGS activity in vivo through an interaction with the N-terminal domain of the enzyme and that removal of this domain can suppress this regulation.
authors.affiliation: Laboratoire de Physiologie Cellulaire Végétale, Institut National de la Recherche Agronomique, Université Joseph Fourier Grenoble I, Grenoble, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Loizeau
authors.forename: Bernadette
authors.initials: B
authors.lastname: Gambonnet
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Zhang
authors.forename: Gilles
authors.initials: G
authors.lastname: Curien
authors.forename: Samuel
authors.initials: S
authors.lastname: Jabrin
authors.forename: Dominique
authors.initials: D
authors.lastname: Van Der Straeten
authors.forename: Willy E
authors.initials: WE
authors.lastname: Lambert
authors.forename: Fabrice
authors.initials: F
authors.lastname: Rébeillé
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ravanel
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000187:drug effects / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D019757:Carbon-Oxygen Lyases / Q000235:genetics* / Q000378:metabolism; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005492:Folic Acid / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000494:pharmacology; D018506:Gene Expression Regulation, Plant; D008715:Methionine / Q000096:biosynthesis; D008969:Molecular Sequence Data
chemical_list: D005493:Folic Acid Antagonists; D002244:Carbon; D005492:Folic Acid; D008715:Methionine; C022696:O-succinylhomoserine (thiol)-lyase; D019757:Carbon-Oxygen Lyases; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase