MTD submitter_name sun shibo MTD submitter_email 2426958342@qq.com MTD submitter_affiliation Hebei University of Technology MTD submitter_pride_login 2426958342@qq.com MTD lab_head_name [test]zhang san MTD lab_head_email test@qq.com MTD lab_head_affiliation [test]test test test test test test test test test test test test test test test test test test test test test test test MTD project_title [test]this is test Mitochondrial glutamine import sustains mitochondrial translation independent of glutaminolysis in cancer MTD project_description [test]Oxidative 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. MTD keywords [test]SLC1A5var, Glutamine, Glutaminolysis, Mitochondrial Glutamine Import, Mitochondrial Translation MTD sample_processing_protocol [test]this is test.testtesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttest MTD data_processing_protocol [test]this is test.testtesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttesttest MTD experiment_type [PRIDE, PRIDE:0000427, Top-down proteomics, ] MTD submission_type COMPLETE MTD species [NEWT, 9606, Homo sapiens (Human), ] MTD tissue [BTO, BTO:0000121, bile, ] MTD instrument [MS, MS:1002523, Q Exactive HF, ] MTD modification [PRIDE, PRIDE:0000398, No PTMs are included in the dataset, ] FMH file_id file_type file_path file_mapping FME 0 OTHER /private/var/folders/fy/pyfy7lzn1psc9dc28gm4sh7m0000gn/T/hsperfdata_sun/checksum.txt FME 3 RAW /Users/sun/iprox/PRIDE/Exploris0057224-DXY-LFM-20250915-ZLZ-A1.raw FME 4 PEAK /Users/sun/iprox/PRIDE/example.mgf FME 5 RESULT /Users/sun/iprox/PRIDE/example.mztab SMH file_id species tissue cell_type disease modification instrument quantification experimental_factor SME 5 [NEWT, 9606, Homo sapiens (Human), ] [BTO, BTO:0000121, bile, ] [PRIDE, PRIDE:0000398, No PTMs are included in the dataset, ] [MS, MS:1002523, Q Exactive HF, ] Not provided COM Version:2.11.1 COM Dataset License:CC0 COM Operating System:Mac OS X 13.7.6 (aarch64)