PXD058312

PXD058312 is an original dataset announced via ProteomeXchange.

Title	SLC25A38 is Required for Mitochondrial Pyridoxal 5’-Phosphate (PLP) accumulation
Description	Many essential proteins require pyridoxal 5’-phosphate (PLP), the active form of vitamin B6, as a cofactor for activity including enzymes important for amino acid metabolism, one-carbon metabolism, polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third of all mammalian PLP-dependent enzymes are localized in the mitochondria; however, the molecular machinery involved in the regulation of mitochondrial PLP levels in mammals remains unknown. Here, we used a genome-wide CRISPRi screen in erythroleukemia cells and organellar metabolomics to identify SLC25A38, a mitochondrial inner membrane protein, as a novel regulator of mitochondrial PLP. SLC25A38 loss causes depletion of mitochondrial, but not cellular, PLP, and impairs cellular proliferation under both physiological and low vitamin B6 conditions. Metabolic changes associated with SLC25A38 loss suggest impaired mitochondrial PLP-dependent enzymatic reactions, including serine to glycine conversion catalyzed by SHMT2 as well as ornithine aminotransferase (OAT). The proliferation defect of SLC25A38-null K562 cells in physiological and low B6 media can be explained by loss of SHMT2-dependent production of one-carbon units and downstream de novo nucleotide synthesis. Our work points to a role for SLC25A38 in mitochondrial PLP maintenance and provides insights into the pathology of congenital sideroblastic anemia
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_05:32:03.765.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shveta Bathla
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-26 22:57:33	ID requested
⏵ 1	2025-05-07 05:32:04	announced

Pena IA, Shi JS, Chang SM, Yang J, Block S, Adelmann CH, Keys HR, Ge P, Bathla S, Witham IH, Sienski G, Nairn AC, Sabatini DM, Lewis CA, Kory N, Vander Heiden MG, Heiman M, SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. Nat Commun, 16(1):978(2025) [pubmed]

10.1038/s41467-025-56130-3;

submitter keyword: SLC25A38,Mito IP,proliferation defects, LC-MS/MS

Myriam Heiman
contact affiliation	MIT
contact email	mheiman@mit.edu
lab head
Shveta Bathla
contact affiliation	Yale university
contact email	shveta.bathla@yale.edu
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/2025/05/PXD058312

PRIDE project URI

• PRIDE
  1. PXD058312
     1. Label: PRIDE project
     2. Name: SLC25A38 is Required for Mitochondrial Pyridoxal 5’-Phosphate (PLP) accumulation