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PXD058312

PXD058312 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSLC25A38 is Required for Mitochondrial Pyridoxal 5’-Phosphate (PLP) accumulation
DescriptionMany 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
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-07_05:32:03.765.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterShveta Bathla
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-11-26 22:57:33ID requested
12025-05-07 05:32:04announced
Publication List
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;
Keyword List
submitter keyword: SLC25A38,Mito IP,proliferation defects, LC-MS/MS
Contact List
Myriam Heiman
contact affiliationMIT
contact emailmheiman@mit.edu
lab head
Shveta Bathla
contact affiliationYale university
contact emailshveta.bathla@yale.edu
dataset submitter
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Dataset FTP location
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