dc.date.accessioned | 2018-03-16T16:31:41Z | |
dc.date.available | 2018-09-08T22:31:19Z | |
dc.date.created | 2018-01-03T20:45:56Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Malecki, Jedrzej Mieczyslaw Jakobsson, Magnus Ho, Angela Yeuan Yen Moen, Anders Rustan, Arild Falnes, Pål . Uncovering human METTL12 as a mitochondrial methyltransferase that modulates citrate synthase activity through metabolite-sensitive lysine methylation. Journal of Biological Chemistry. 2017, 292(43), 17950-17962 | |
dc.identifier.uri | http://hdl.handle.net/10852/61069 | |
dc.description.abstract | Lysine methylation is an important and much-studied posttranslational modification of nuclear and cytosolic proteins but is present also in mitochondria. However, the responsible mitochondrial lysine-specific methyltransferases (KMTs) remain largely elusive. Here, we investigated METTL12, a mitochondrial human S-adenosylmethionine (AdoMet)-dependent methyltransferase and found it to methylate a single protein in mitochondrial extracts, identified as citrate synthase (CS). Using several in vitro and in vivo approaches, we demonstrated that METTL12 methylates CS on Lys-395, which is localized in the CS active site. Interestingly, the METTL12-mediated methylation inhibited CS activity and was blocked by the CS substrate oxaloacetate. Moreover, METTL12 was strongly inhibited by the reaction product S-adenosylhomocysteine (AdoHcy). In summary, we have uncovered a novel human mitochondrial KMT that introduces a methyl modification into a metabolic enzyme and whose activity can be modulated by metabolic cues. Based on the established naming nomenclature for similar enzymes, we suggest that METTL12 be renamed CS-KMT (gene name CSKMT).
This research was originally published in the Journal of Biological Chemistry. © 2017 American Society for Biochemistry and Molecular Biology | en_US |
dc.language | EN | |
dc.title | Uncovering human METTL12 as a mitochondrial methyltransferase that modulates citrate synthase activity through metabolite-sensitive lysine methylation | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Malecki, Jedrzej Mieczyslaw | |
dc.creator.author | Jakobsson, Magnus | |
dc.creator.author | Ho, Angela Yeuan Yen | |
dc.creator.author | Moen, Anders | |
dc.creator.author | Rustan, Arild | |
dc.creator.author | Falnes, Pål | |
cristin.unitcode | 185,15,29,0 | |
cristin.unitname | Institutt for biovitenskap | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1535283 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Biological Chemistry&rft.volume=292&rft.spage=17950&rft.date=2017 | |
dc.identifier.jtitle | Journal of Biological Chemistry | |
dc.identifier.volume | 292 | |
dc.identifier.issue | 43 | |
dc.identifier.startpage | 17950 | |
dc.identifier.endpage | 17962 | |
dc.identifier.doi | http://dx.doi.org/10.1074/jbc.M117.808451 | |
dc.identifier.urn | URN:NBN:no-63688 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0021-9258 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/61069/1/Malecki-METTL12-final.pdf | |
dc.type.version | PublishedVersion | |