PXD058312 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-11-26 22:57:33 | ID requested | |
⏵ 1 | 2025-05-07 05:32:04 | announced | |
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 affiliation | MIT |
contact email | mheiman@mit.edu |
lab head | |
Shveta Bathla |
contact affiliation | Yale university |
contact email | shveta.bathla@yale.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD058312
- Label: PRIDE project
- Name: SLC25A38 is Required for Mitochondrial Pyridoxal 5’-Phosphate (PLP) accumulation