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PXD069373-1

PXD069373 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMitochondrial glutamine import sustains mitochondrial translation independent of glutaminolysis in cancer
DescriptionOxidative phosphorylation (OXPHOS) fulfills energy metabolism and biosynthesis through tricarboxylic acid (TCA) cycle and an intact electron transport chain (ETC). Mitochondrial glutamine import (MGI) replenishes TCA cycle through glutaminolysis, but its broader roles in cancer remains unclear. Here we show that MGI sustains OXPHOS independent of glutaminolysis, by maintaining ETC integrity. Exogenous glutamate availability abrogates cellular dependence on glutaminolysis but not SLC1A5var-mediated MGI. Blocking MGI elicits severe mitochondrial defects, reducing mitochondrial glucose oxidation and increasing glutamine reductive carboxylation. MGI but not glutaminolysis is essential for mitochondrial translation by enabling biogenesis of Gln-mt-tRNAGln, the most limiting mitochondrial aminoacyl-tRNA in cancer cells. Finally, deleting SLC1A5 in mice and targeting SLC1A5var in human tumors inhibit Gln-mt-tRNAGln biogenesis, mitochondrial translation and blunt tumor growth. Our findings uncover a previously unrecognized role of MGI in safeguarding mitochondrial translation independent of glutaminolysis, and inform a therapeutic option by targeting MGI to abrogate OXPHOS for cancer treatment.
HostingRepositoryiProX
AnnounceDate2025-09-30
AnnouncementXMLSubmission_2025-10-12_20:23:49.278.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLingzhi Zhu
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Astral
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-10-12 20:23:34ID requested
12025-10-12 20:23:50announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: SLC1A5var, Glutamine, Glutaminolysis, Mitochondrial Glutamine Import, Mitochondrial Translation
Contact List
Fuming Li
contact affiliationFudan University
contact emailfuming_li@fudan.edu.cn
lab head
Lingzhi Zhu
contact affiliationFudan University
contact email24110880028@m.fudan.edu.cn
dataset submitter
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iProX dataset URI