PXD058579-1

PXD058579 is an original dataset announced via ProteomeXchange.

Title	SLC25A45 is required for mitochondrial uptake of methylated basic amino acids and de novo carnitine biosynthesis (Part 2 = Interactome AP-MS Analysis)
Description	Methylated amino acids accumulate upon the degradation of methylated proteins and are implicated in diverse metabolic and signalling pathways. Dimethylarginine inhibits nitric oxide synthase while trimethyllysine is metabolised in a compartmentalised manner to produce the amino acid derivative carnitine. Consequently, disturbed methylated amino acid homeostasis is associated with various disorders including cardiovascular disease and renal failure. Mitochondria are core processing hubs in conventional amino acid metabolism but how they interact with methylated amino acids is unclear. Here, we reveal that the orphan mitochondrial solute carrier SLC25A45 is required for the mitochondrial uptake of dimethylarginine and trimethyllysine. Characterisation of SLC25A45 identified a non-synonymous mutation of SLC25A45 near its C-terminus (R285C) that impacts solute carrier stability and associates with altered plasma methylated amino acid levels and cardiac alterations in men. Metabolic tracing of trimethyllysine reveals that SLC25A45 is essential for the de novo biosynthesis of carnitine. Suppression of SLC25A45 reduces intracellular acetylcarnitine levels and limits histone acetylation in carnitine-synthesising ovarian cancer cells. We propose that SLC25A45 is an essential mediator of compartmentalised methylated amino acid metabolism with diverse cellular roles that include epigenetic control.
HostingRepository	PRIDE
AnnounceDate	2025-10-13
AnnouncementXML	Submission_2025-10-13_01:11:53.907.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-04 10:49:22	ID requested
⏵ 1	2025-10-13 01:11:54	announced

10.1016/J.MOLCEL.2025.08.018;

submitter keyword: Mitochondria, SLC25A45, Methylated basic amino acids

Sara Rossana Zanivan
contact affiliation	CRUK -CRUK Scotland nstitute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom
contact email	s.zanivan@crukscotlandinstitute.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD058579

PRIDE project URI

• PRIDE
  1. PXD058579
     1. Label: PRIDE project
     2. Name: SLC25A45 is required for mitochondrial uptake of methylated basic amino acids and de novo carnitine biosynthesis (Part 2 = Interactome AP-MS Analysis)