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Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit

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.

Type Journal
ISBN 2211-1247 (Electronic)
Authors Picchioni, D.; Antolin-Fontes, A.; Camacho, N.; Schmitz, C.; Pons-Pons, A.; Rodriguez-Escriba, M.; Machallekidou, A.; Guler, M. N.; Siatra, P.; Carretero-Junquera, M.; Serrano, A.; Hovde, S. L.; Knobel, P. A.; Novoa, E. M.; Sola-Vilarrubias, M.; Kaguni, L. S.; Stracker, T. H.; Ribas de Pouplana, L.
Responsible Garvan Author Dr Eva Maria Novoa Pardo
Publisher Name Cell Reports
Published Date 2019-04-02
Published Volume 27
Published Issue 1
Published Pages 40-47 e5
Status Published in-print
DOI 10.1016/j.celrep.2019.03.022
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/30943413