# Identification of an uncharacterized gene as a mitochondrial methionine tRNA synthetase in Caenorhabditis elegans

## TL;DR

This study identifies a new gene in C. elegans that functions as a mitochondrial methionine tRNA synthetase and shows its role in mitochondrial health.

## Contribution

The paper characterizes a previously uncharacterized gene as a mitochondrial methionine tRNA synthetase in C. elegans.

## Key findings

- The P447V mutation in mars-2 causes a loss-of-function and activates the mitochondrial unfolded protein response.
- Reduced mars-2 activity leads to decreased mitochondrial protein levels and disrupted mitochondrial function.
- The hypomorphic mars-2(P447V) strain is a useful model for studying mitochondrial translation and aaRS function.

## Abstract

Aminoacyl-tRNA synthetases (aaRSs) are essential for translation, as they charge tRNA molecules with their corresponding amino acids. Alterations in aaRSs can significantly disrupt both cytosolic and mitochondrial translation. Through a forward genetic screen for mitochondrial unfolded protein response (UPRmt) activators in Caenorhabditis elegans, we identified a missense mutation (P447V) in the previously uncharacterized gene Y105E8A.20, which encodes for a methionine tRNA synthetase (MetRS). Here, we characterize the UPRmt induction by Y105E8A.20, which we call mars-2, and demonstrate that the P447V allele is a loss-of-function mutation. Furthermore, we show that impaired mars-2 activity leads to reduced mitochondrial-encoded protein abundance, depletion of mitochondrial membrane potential, fragmented mitochondrial morphology, and mild developmental delay, although the animals remain viable. Hence, this hypomorphic mars-2(P447V) strain provides a valuable tool for studying mitochondrial translation and understanding how aaRSs are involved in mitochondrial homeostasis.