title: Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase.
abstract: The protein methylome in mammalian mitochondria has been little studied until recently. Here, we describe that lysine-368 of human citrate synthase is methylated and that the modifying enzyme, localized in the mitochondrial matrix, is methyltransferase-like protein 12 (METTL12), a member of the family of 7β-strand methyltransferases. Lysine-368 is near the active site of citrate synthase, but removal of methylation has no effect on its activity. In mitochondria, it is possible that some or all of the enzymes of the citric acid cycle, including citrate synthase, are organized in metabolons to facilitate the channelling of substrates between participating enzymes. Thus, possible roles for the methylation of Lys-368 are in controlling substrate channelling itself, or in influencing protein-protein interactions in the metabolon.
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK.
authors.forename: Virginie F
authors.initials: VF
authors.lastname: Rhein
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Carroll
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK.
authors.forename: Shujing
authors.initials: S
authors.lastname: Ding
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Fearnley
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK.
authors.forename: John E
authors.initials: JE
authors.lastname: Walker
mesh_terms: D000595:Amino Acid Sequence; D064113:CRISPR-Cas Systems; D020134:Catalytic Domain; D002950:Citrate (si)-Synthase / Q000737:chemistry / Q000378:metabolism*; D019295:Computational Biology; D017124:Conserved Sequence; D016368:Frameshift Mutation; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013499:Surface Properties
chemical_list: D011993:Recombinant Fusion Proteins; C000622695:CSKMT protein, human; D008780:Methyltransferases; D002950:Citrate (si)-Synthase; D008239:Lysine
keywords: METTL12; citrate synthase; metabolons; mitochondria; protein methylation; substrate channelling