Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit
Summary: 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 unk...
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Elsevier
2019-04-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719303298 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daria Picchioni Albert Antolin-Fontes Noelia Camacho Claus Schmitz Alba Pons-Pons Marta Rodríguez-Escribà Antigoni Machallekidou Merve Nur Güler Panagiota Siatra Maria Carretero-Junquera Alba Serrano Stacy L. Hovde Philip A. Knobel Eva M. Novoa Maria Solà-Vilarrubias Laurie S. Kaguni Travis H. Stracker Lluís Ribas de Pouplana |
spellingShingle |
Daria Picchioni Albert Antolin-Fontes Noelia Camacho Claus Schmitz Alba Pons-Pons Marta Rodríguez-Escribà Antigoni Machallekidou Merve Nur Güler Panagiota Siatra Maria Carretero-Junquera Alba Serrano Stacy L. Hovde Philip A. Knobel Eva M. Novoa Maria Solà-Vilarrubias Laurie S. Kaguni Travis H. Stracker Lluís Ribas de Pouplana Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit Cell Reports |
author_facet |
Daria Picchioni Albert Antolin-Fontes Noelia Camacho Claus Schmitz Alba Pons-Pons Marta Rodríguez-Escribà Antigoni Machallekidou Merve Nur Güler Panagiota Siatra Maria Carretero-Junquera Alba Serrano Stacy L. Hovde Philip A. Knobel Eva M. Novoa Maria Solà-Vilarrubias Laurie S. Kaguni Travis H. Stracker Lluís Ribas de Pouplana |
author_sort |
Daria Picchioni |
title |
Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit |
title_short |
Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit |
title_full |
Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit |
title_fullStr |
Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit |
title_full_unstemmed |
Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit |
title_sort |
mitochondrial protein synthesis and mtdna levels coordinated through an aminoacyl-trna synthetase subunit |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-04-01 |
description |
Summary: 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. : Picchioni et al. report the architecture of a housekeeping enzyme that is essential for mitochondrial protein synthesis. This enzyme is a heterodimer that contains a catalytically active subunit and an inactive but essential monomer (SLIMP). SLIMP also interacts with a major mitochondrial protease to control mitochondrial DNA levels. Keywords: seryl-tRNA synthetase, LON, tRNA, mtDNA, mitochondria, translation, replication |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719303298 |
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doaj-4bd6ef76423646f5a93ac1cb397bb7ac2020-11-24T20:44:19ZengElsevierCell Reports2211-12472019-04-012714047.e5Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase SubunitDaria Picchioni0Albert Antolin-Fontes1Noelia Camacho2Claus Schmitz3Alba Pons-Pons4Marta Rodríguez-Escribà5Antigoni Machallekidou6Merve Nur Güler7Panagiota Siatra8Maria Carretero-Junquera9Alba Serrano10Stacy L. Hovde11Philip A. Knobel12Eva M. Novoa13Maria Solà-Vilarrubias14Laurie S. Kaguni15Travis H. Stracker16Lluís Ribas de Pouplana17Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainStructural MitoLab, Department of Structural Biology, Molecular Biology Institute Barcelona (IBMB-CSIC), Barcelona, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainDepartment of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, USAInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, Spain; Laboratory for Molecular Radiobiology, Clinic of Radiation Oncology, University of Zurich, 8057 Zurich, SwitzerlandCentre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology (BIST), Doctor Aiguader 88, 08003 Barcelona, Spain; Garvan Institute of Medical Research, 384 Victoria Street, 2010 Darlinghurst, NSW, AustraliaStructural MitoLab, Department of Structural Biology, Molecular Biology Institute Barcelona (IBMB-CSIC), Barcelona, SpainDepartment of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, USA; Institute of Biosciences and Medical Technology, University of Tampere, 33014 Tampere, FinlandInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, SpainInstitute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Parc Científic de Barcelona, C/Baldiri Reixac 10, 08028 Barcelona, Catalonia, Spain; Catalan Institution for Research and Advanced Studies (ICREA), P/Lluis Companys 23, 08010 Barcelona, Catalonia, Spain; Corresponding authorSummary: 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. : Picchioni et al. report the architecture of a housekeeping enzyme that is essential for mitochondrial protein synthesis. This enzyme is a heterodimer that contains a catalytically active subunit and an inactive but essential monomer (SLIMP). SLIMP also interacts with a major mitochondrial protease to control mitochondrial DNA levels. Keywords: seryl-tRNA synthetase, LON, tRNA, mtDNA, mitochondria, translation, replicationhttp://www.sciencedirect.com/science/article/pii/S2211124719303298 |