# Specific SLC25 carriers regulate mitochondrial protein synthesis

## TL;DR

This study shows that specific mitochondrial carrier proteins from the SLC25 family are crucial for regulating mitochondrial protein synthesis and function.

## Contribution

The paper identifies specific SLC25 carriers and their roles in mitochondrial translation and energy function through genome-wide and multiomic analyses.

## Key findings

- SLC25A25, SLC25A44, SLC25A45, and SLC25A48 are essential for mitochondrial translation and oxidative phosphorylation.
- SLC25A48 is stabilized by choline and is involved in choline transport and mitochondrial membrane remodeling.
- Impaired transport of specific metabolites disrupts mitochondrial function and structure.

## Abstract

A genome-wide knockout screen identified members of the SLC25 family of mitochondrial carrier proteins as important regulators of the rate of de novo mitochondrial protein synthesis. To elucidate this relationship, we generated human cell knockouts for SLC25A25, SLC25A44, SLC25A45, and SLC25A48, which have been shown to exchange adenosine triphosphate-magnesium (ATP-Mg) and phosphate, branched-chain amino acids, methylated basic amino acids, and choline, respectively. Multiomic and functional analyses identified that these four carriers are crucial for mitochondrial translation, biogenesis and function of the oxidative phosphorylation system, as well as mitochondrial morphology. Thermostability screens showed that SLC25A48 is specifically stabilized by choline, and changes in the mitochondrial metabolome and lipidome indicated defects in choline biosynthetic pathways and remodeling of mitochondrial membranes, both consistent with SLC25A48 being a choline transporter. These results highlight the essential roles of specific SLC25 transporters in maintaining mitochondrial structure and function and show that impaired transport of branched-chain amino acids, methylated basic amino acids, ATP-Mg, and choline affects mitochondrial translation.

Mitochondrial carrier proteins control protein synthesis, dynamics, and energy function through selective metabolite transport.