PXD066637-1

PXD066637 is an original dataset announced via ProteomeXchange.

Title	SLC25-family transporters of choline and branched-chain and methylated amino acids regulate mitochondrial protein synthesis
Description	Genome-wide knock out 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 ATP and magnesium, 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 stabilised by choline and changes in the mitochondrial metabolome and lipidome indicated defects in choline biosynthetic pathways and remodelling 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 of mitochondrial translation is sensitive to local concentrations of branched chain amino acids, methylated basic amino acids, ATP, magnesium and choline.
HostingRepository	PRIDE
AnnounceDate	2025-12-19
AnnouncementXML	Submission_2025-12-18_16:48:42.160.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Timothy McCubbin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-27 21:06:00	ID requested
⏵ 1	2025-12-18 16:48:42	announced

Dataset with its publication pending

submitter keyword: omics, metabolite transport,transporters, lipidomics, mitochondria, energy metabolism

Aleksandra Filipovska
contact affiliation	The Kids Research Institute Australia, Northern Entrance, Perth Children’s Hospital, 15 Hospital Avenue, Nedlands, Western Australia, 6009, Australia
contact email	aleksandra.filipovska@uwa.edu.au
lab head
Timothy McCubbin
contact affiliation	University of Queensland
contact email	t.mccubbin@uq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066637
     1. Label: PRIDE project
     2. Name: SLC25-family transporters of choline and branched-chain and methylated amino acids regulate mitochondrial protein synthesis