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PXD049224

PXD049224 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia
DescriptionNME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.
HostingRepositoryPRIDE
AnnounceDate2026-02-23
AnnouncementXMLSubmission_2026-02-22_16:14:36.755.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYi-Ju Chen
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-06 23:50:46ID requested
12026-02-22 16:14:37announced
Publication List
Chen CW, Su C, Huang CY, Huang XR, Cuili X, Chao T, Fan CH, Ting CW, Tsai YW, Yang KC, Yeh TY, Hsieh ST, Chen YJ, Feng Y, Hunter T, Chang ZF, NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia. Nat Commun, 15(1):2264(2024) [pubmed]
10.1038/s41467-024-46385-7;
Keyword List
submitter keyword: hypoxia,NME3, mitochondria, mouse, LC-MS/MS
Contact List
Zee-Fen Chang
contact affiliationInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
contact emailzfchang@ntu.edu.tw
lab head
Yi-Ju Chen
contact affiliationNational Yang Ming Chiao Tung University
contact emailtp7249@gmail.com
dataset submitter
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Dataset FTP location
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