Mitochondrial protein synthesis and mtDNA levels coordinated through an aminoacyl-tRNA synthetase subunit

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  • dc.contributor.author Picchioni, Daria
  • dc.contributor.author Antolin-Fontes, Albert
  • dc.contributor.author Camacho, Noelia
  • dc.contributor.author Schmitz, Claus
  • dc.contributor.author Pons-Pons, Alba
  • dc.contributor.author Rodríguez-Escribà, Marta
  • dc.contributor.author Machallekidou, Antoni
  • dc.contributor.author Güler, Merve Nur
  • dc.contributor.author Siatra, Panagiota
  • dc.contributor.author Carretero-Junquera, Maria
  • dc.contributor.author Serrano, Alba
  • dc.contributor.author Hovde, Stacy L.
  • dc.contributor.author Knobel, Philip A.
  • dc.contributor.author Novoa, Eva Maria
  • dc.contributor.author Solà-Vilarrubias, Maria
  • dc.contributor.author Kaguni, Laurie S.
  • dc.contributor.author Stracker, Travis
  • dc.contributor.author Ribas de Pouplana, Lluís
  • dc.date.accessioned 2019-07-16T09:27:19Z
  • dc.date.available 2019-07-16T09:27:19Z
  • dc.date.issued 2019
  • dc.description.abstract The aminoacylation of tRNAs by aminoacyl-tRNA synthetases (ARSs) is a central reaction in biology. Multiple regulatory pathways use the aminoacylation status of cytosolic tRNAs to monitor and regulate metabolism. The existence of equivalent regulatory networks within the mitochondria is unknown. Here, we describe a functional network that couples protein synthesis to DNA replication in animal mitochondria. We show that a duplication of the gene coding for mitochondrial seryl-tRNA synthetase (SerRS2) generated in arthropods a paralog protein (SLIMP) that forms a heterodimeric complex with a SerRS2 monomer. This seryl-tRNA synthetase variant is essential for protein synthesis and mitochondrial respiration. In addition, SLIMP interacts with the substrate binding domain of the mitochondrial protease LON, thus stimulating proteolysis of the DNA-binding protein TFAM and preventing mitochondrial DNA (mtDNA) accumulation. Thus, mitochondrial translation is directly coupled to mtDNA levels by a network based upon a profound structural modification of an animal ARS.
  • dc.description.sponsorship This work was supported by grants SVP2014-068398 and BIO2015-64572 from the Spanish Ministry of Economy and Competitiveness (to L.R.d.P.). This work used the platforms of the Grenoble Instruct Centre (ISBG; UMS 3518 CNRS-CEA-UJF-EMBL) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01) within the Grenoble Partnership for Structural Biology (PSB)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Picchioni D, Antolin-Fontes A, Camacho N, Schmitz C, Pons-Pons A, Rodríguez-Escribà M et al. Mitochondrial protein synthesis and mtDNA levels coordinated through an aminoacyl-tRNA synthetase subunit. Cell Rep. 2019 Apr 2; 27(1): 40-47.e5. DOIi: 10.1016/j.celrep.2019.03.022
  • dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2019.03.022
  • dc.identifier.issn 2211-1247
  • dc.identifier.uri http://hdl.handle.net/10230/42003
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Cell Reports. 2019 Apr 2;27(1):40-7
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SVP2014-068398
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2015-64572
  • dc.rights © 2019 The Authors. This is an open access article under a CC BY-NC-ND license
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.other Mitocondris
  • dc.subject.other ADN mitocondrial
  • dc.subject.other RNA
  • dc.title Mitochondrial protein synthesis and mtDNA levels coordinated through an aminoacyl-tRNA synthetase subunit
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion