The team headed by ICREA researcher, Lluís Ribas, has published a study in Cell Report describing a functional network that coordinates protein synthesis and DNA replication in animal mitochondria.
These findings contribute to our understanding of the mechanisms involved in mitochondrial dysregulation associated with diseases such as MELAS and MERRF and may help to identify new therapeutic approaches.
A study by researcher Lluís Ribas from the Gene Translation Laboratory at the Institute for Research in Biomedicine (IRB Barcelona) and published in Cell Reports furthers understanding of the role played by the essential protein SLIMP in coordination the synthesis of mitochondrial mass.
A collaboration between IRB Barcelona and IBMB-CSIC researchers Travis Stracker and Maria Solà-Vilarubias, respectively, the study describes a functional network that combines protein synthesis with DNA replication in animal mitochondria. Until now, the presence of regulatory networks within mitochondria was unknown.
“We have been studying the functions of the essential mitochondrial protein SLIMP since discovering it back in 2010. These results are a step forward and will help us to identify the relevant mitochondrial regulatory mechanisms for cell metabolism and growth control. Many human diseases are caused by or cause mitochondrial dysregulation, and understanding the mechanisms involved will help to identify new therapeutic approaches,” explains Ribas, ICREA researcher at IRB Barcelona.
The study demonstrates that the duplication of a gene encoding mitochondrial seryl-tRNA synthatase (SerRS2) in arthropods produces a paralogue protein (SLIMP), which forms a heterodimeric complex enriched in a monomer of SerRS2, thereby producing a new variant of SerRS2 that is essential for protein synthesis and mitochondrial respiration.
This work also reveals that SLIMP interacts simultaneously with the mitochondrial protease LON, thus stimulating the degradation of the DNA binding protein TFAM (Mitochondrial transcription factor A), and preventing the accumulation of mitochondrial DNA. Therefore, mitochondria protein synthesis is coupled directly to levels of mitochondrial DNA via a network based on a profound structural modification of animal ARS.
Daria Picchioni, Albert Antolin-Fontes, Noelia Camacho, Claus Schmitz, Alba Pons-Pons, Marta Rodríguez-Escribà, Antigoni Machallekidou, Merve Nur Guler, 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, and Lluís Ribas de Pouplana.
Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit
Cell Reports (2019) DOI: 10.1016/j.celrep.2019.03.022