Files and links (1)
CC BY V4.0, Open Access
Journal article
Specific SLC25 carriers regulate mitochondrial protein synthesis
Science advances, Vol.12(9), eaeb0049
2026
PMID: 41739937
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.
Details
- Title
- Specific SLC25 carriers regulate mitochondrial protein synthesis
- Authors/Creators
- Danielle L. Rudler - The University of Western AustraliaLaetitia A. Hughes - The University of Western AustraliaMartin S. King - MRC Mitochondrial Biology UnitJessica Baker - Princess Margaret Hospital for ChildrenRichard G. Lee - The University of Western AustraliaAndrianto P. Gandadireja - The University of Western AustraliaAnisha Sunil - The University of Western AustraliaSamuel V. Fagan - The University of Western AustraliaBlake Payne - The University of Western AustraliaNicola Gray - Murdoch University, Centre for Computational and Systems MedicineTim McCubbin - The University of QueenslandEdmund R. S. Kunji - MRC Mitochondrial Biology UnitOliver Rackham - The University of Western AustraliaAleksandra Filipovska - The University of Western Australia
- Publication Details
- Science advances, Vol.12(9), eaeb0049
- Publisher
- American Association for the Advancement of Science
- Number of pages
- 17
- Identifiers
- 991005869304807891
- Copyright
- © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
- Murdoch Affiliation
- Australian National Phenome Centre; Centre for Computational and Systems Medicine
- Language
- English
- Resource Type
- Journal article
Metrics
1 File views/ downloads
1 Record Views