title: Plants Possess a Cyclic Mitochondrial Metabolic Pathway similar to the Mammalian Metabolic Repair Mechanism Involving Malate Dehydrogenase and l-2-Hydroxyglutarate Dehydrogenase.
abstract: Enzymatic side reactions can give rise to the formation of wasteful and toxic products that are removed by metabolite repair pathways. In this work, we identify and characterize a mitochondrial metabolic repair mechanism in Arabidopsis thaliana involving malate dehydrogenase (mMDH) and l-2-hydroxyglutarate dehydrogenase (l-2HGDH). We analyze the kinetic properties of both A. thaliana mMDH isoforms, and show that they produce l-2-hydroxyglutarate (l-2HG) from 2-ketoglutarate (2-KG) at low rates in side reactions. We identify A. thaliana l-2HGDH as a mitochondrial FAD-containing oxidase that converts l-2HG back to 2-KG. Using loss-of-function mutants, we show that the electrons produced in the l-2HGDH reaction are transferred to the mitochondrial electron transport chain through the electron transfer protein (ETF). Thus, plants possess the biochemical components of an l-2HG metabolic repair system identical to that found in mammals. While deficiencies in the metabolism of l-2HG result in fatal disorders in mammals, accumulation of l-2HG in plants does not adversely affect their development under a range of tested conditions. However, orthologs of l-2HGDH are found in all examined genomes of viridiplantae, indicating that the repair reaction we identified makes an essential contribution to plant fitness in as yet unidentified conditions in the wild.
authors.affiliation: Institute of Developmental and Molecular Biology of Plants, Plant Molecular Physiology and Biotechnology Group, Heinrich-Heine-Universität, and Cluster of Excellence on Plant Sciences (CEPLAS), Universitätsstraße 1, D-40225 Düsseldorf, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Hüdig
authors.affiliation: Institute of Developmental and Molecular Biology of Plants, Plant Molecular Physiology and Biotechnology Group, Heinrich-Heine-Universität, and Cluster of Excellence on Plant Sciences (CEPLAS), Universitätsstraße 1, D-40225 Düsseldorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Maier
authors.affiliation: Institute of Developmental and Molecular Biology of Plants, Plant Molecular Physiology and Biotechnology Group, Heinrich-Heine-Universität, and Cluster of Excellence on Plant Sciences (CEPLAS), Universitätsstraße 1, D-40225 Düsseldorf, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Scherrers
authors.affiliation: Institute of Developmental and Molecular Biology of Plants, Plant Molecular Physiology and Biotechnology Group, Heinrich-Heine-Universität, and Cluster of Excellence on Plant Sciences (CEPLAS), Universitätsstraße 1, D-40225 Düsseldorf, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Seidel
authors.affiliation: Metabolic Unit, Clinical Chemistry, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Erwin E W
authors.initials: EE
authors.lastname: Jansen
authors.affiliation: Institute of Plant Biochemistry, Heinrich-Heine-Universität, Universitätsstraße 1, and Cluster of Excellence on Plant Sciences (CEPLAS), D-40225 Düsseldorf, Germany.
authors.forename: Tabea
authors.initials: T
authors.lastname: Mettler-Altmann
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Martin K M
authors.initials: MK
authors.lastname: Engqvist
authors.affiliation: Institute of Developmental and Molecular Biology of Plants, Plant Molecular Physiology and Biotechnology Group, Heinrich-Heine-Universität, and Cluster of Excellence on Plant Sciences (CEPLAS), Universitätsstraße 1, D-40225 Düsseldorf, Germany veronica.maurino@uni-duesseldorf.de.
authors.forename: Veronica G
authors.initials: VG
authors.lastname: Maurino
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D004579:Electron Transport; D004583:Electrons; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D018506:Gene Expression Regulation, Plant; D005977:Glutarates; D007656:Ketoglutaric Acids; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D029681:Arabidopsis Proteins; D004269:DNA, Bacterial; D005977:Glutarates; D007656:Ketoglutaric Acids; D011994:Recombinant Proteins; C036483:T-DNA; C019417:alpha-hydroxyglutarate; D000429:Alcohol Oxidoreductases; D008291:Malate Dehydrogenase; C023858:2-hydroxyglutarate dehydrogenase
keywords: Arabidopsis; Malate dehydrogenase; Metabolite repair; l-2-Hydroxyglutarate; l-2-Hydroxyglutarate dehydrogenase