| Title: |
Specific SLC25 carriers regulate mitochondrial protein synthesis |
| Authors: |
Rudler, Danielle L.; Hughes, Laetitia A.; King, Martin S.; Baker, Jessica; Lee, Richard G.; Gandadireja, Andrianto P.; Sunil, Anisha; Fagan, Samuel V.; Payne, Blake; Gray, Nicola; McCubbin, Tim; Kunji, Edmund R. S.; Rackham, Oliver; Filipovska, Aleksandra |
| Publisher Information: |
American Association for the Advancement of Science |
| Publication Year: |
2026 |
| Subject Terms: |
Biochemistry; Biomedicine and Life Sciences; Cell Biology; SciAdv r-articles |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
pdf |
| Language: |
English |
| Relation: |
ispartof: Science advances issue 9 vol 12; WOS:001699289700007; 991005869304807891; https://researchportal.murdoch.edu.au/view/delivery/61MUN_INST/12192798930007891/13192798920007891; alma:61MUN_INST/bibs/991005869304807891 |
| DOI: |
10.1126/sciadv.aeb0049 |
| Availability: |
https://doi.org/10.1126/sciadv.aeb0049; https://researchportal.murdoch.edu.au/esploro/outputs/journalArticle/Specific-SLC25-carriers-regulate-mitochondrial-protein/991005869304807891; https://researchportal.murdoch.edu.au/view/delivery/61MUN_INST/12192798930007891/13192798920007891 |
| Rights: |
© 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. ; Open ; CC BY V4.0 |
| Accession Number: |
edsbas.FEB266FF |
| Database: |
BASE |