Meeting the needs of mitochondrial translation

Why do the mitochondria import tRNAs from the cell’s cytosol? If we take the example of the green microalgae Chlamydomonas reinhardtii, the reason is quite clear: “Only three genes code for the tRNAs in the mitochondrial DNA of ‘Chlamy’ and yet we know that there need to be at least 20 to ensure the translation”, Claire Remacle explains. As a result, the question scientists are asking is: what regulates this import? The mechanisms that control this movement of tRNAs from the cytosol to the mitochondria are still unknown.

In 2009, Claire Remacle’s team, in collaboration with the researchers from the Institut de Biologie Moléculaire des Plantes (IBMP) in Strasbourg, showed that the tRNAs that are imported into Chlamy's mitochondria are directly linked to the use of codons in the mitochondrial DNA (1). “This means that what is imported is strictly regulated. There is a correlation between the nature and the quantity of the imported tRNAs and the tRNAs the mitochondria need for the translation”, Claire Remacle specifies.

In this case, would the import of tRNAs be a dynamic process that adapts to the contents of the mitochondrial DNA? Does the latter send signals that manage the import of the tRNAs? To test this hypothesis, Claire Remacle and Thalia Salinas, a Marie Curie post-doctoral researcher at the laboratory of genetics of microorganisms at ULg, changed the use of the codons within the mitochondrial genome. “We replaced a significantly used codon for the amino acid, glycine, by a less used codon", Claire Remacle points out.

The tRNA pool, a key factor in the success of the translation

Still in collaboration with the IBMP in Strasbourg and other researchers in their department (Professor Patrick Motte), the two scientists analysed the consequences of this slight transformation in Chlamydomonas reinhardtii. “The microalgae didn’t like this manipulation because we observed a decrease in the translation and respiratory activity in the mitochondria”, Claire Remacle reveals. According to the latter, these effects are the result of a modification in the tRNA pool available in the mitochondria. Hence, the import of tRNAs in the mitochondria isn’t a dynamic process that adapts to the contents of the mitochondrial DNA. Instead, these works published in PLoS Genetics (2) suggest that the level of tRNAs imported into the mitochondria results from a co-evolving adaptation between the tRNA import mechanism and the needs of the mitochondria to make their translation machinery work. “The new concept here is that our results imply that the tRNA pool in the mitochondria and the use of the codons have evolved together”, Claire Remacle summarises.

This highly fundamental research and the resulting discoveries could, however, serve in the most applied fields. “Laboratories are currently attempting to increase gene expression in algae chloroplasts to produce antibodies or products with a high added value”, Claire Remacle continues. “Our works demonstrate that we have to pay attention to how the codons are used and that it isn’t enough to replace the little-used codons with significantly-used codons to increase the translation. It is the balance between the tRNAs which is important in not disrupting the translation rather than the “power” of the codon”. Indeed, following the transformation that occurred in Chlamy, even though the researchers only changed the codons for one gene, they observed disruptions in the translation of six genes present in the mitochondrial genome!

(1) Elizaveta Vinogradova,Thalia Salinas, Valérie Cognat, Claire Remacle, and Laurence Maréchal-Drouard. Steady-state of imported tRNAs in Chlamydomonas mitochondria are correlated with both cytosolic and mitochondrial codon usages. Nucleic Acids Res. 2009 April; 37(5): 1521–1528. Published online 2009 April. doi:  10.1093/nar/gkn1073.

(2) Thalia Salinas, Francéline Duby, Véronique Larosa, Nadine Coosemans, Nathalie Bonnefoy, Patrick Motte, Laurence Maréchal-Drouard, Claire Remacle. Co-Evolution of Mitochondrial tRNA Import and Codon Usage Determines Translational Efficiency in the Green Alga Chlamydomonas. PLoS Genet. 2012 Sep;8(9):e1002946. doi: 10.1371/journal.pgen.1002946. Epub 2012 Sep 20.