{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/report.log_dataset3.txt","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/report.log_dataset2.txt"],"Xml":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/mqpar_dataset1.xml"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/LC-MS_files_dataset3.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/LC-MS_files_dataset1.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/LC-MS_dataset2.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/txt_dataset1.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/report_dataset2.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/10/PXD069822/report_dataset3.zip"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"labhead_mail":["t.a.nyman@medisin.uio.no"],"submitter":["Ingrid Maria Erika Ekman Stensland"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics","Data-independent acquisition"],"software":["Not available"],"submitter_keywords":["Mitochondria","innate immunity","protein synthesis","metabolism","Mitochondria; aging; protein synthesis; innate immunity; metabolism","aging"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD069822"],"tissue":["Bone Marrow Macrophage","Embryonic Fibroblast"],"sample_protocol":["Two sets of samples were subjected to proteomics analysis: mouse embryonic fibroblasts (MEFs)  homozygous for wild type Polgwt or the PolgD257A variant treated with and without chloramphenicol (124M) (dataset1); MEFs homozygous for wild type Polgwt treated with and without chloramphenicol (124M) (dataset2);  and bone marrow derived macrophages (BMDM) homozygous for wild type Polgwt or the PolgD257A variant treated with and without chloramphenicol (124M) (dataset3).The proteins were precipitated on amine beads as previously described (PMID 30833379). The precipitated proteins on beads were dissolved in 50 mM ammonium bicarbonate, reduced, alkylated and digested with trypsin (1:50 enzyme:protein ratio; Promega, United States) at 37°C overnight. The resulting peptide mixture was purified by STAGE-TIP method using a C18 resin disk (3M Empore) before the samples were analysed by a nanoLC-MS/MS using nanoElute coupled to timsTOF PRO2 (Bruker) with 60 minute separation gradient and 25cm Aurora C18 column. The timsTOF PRO2 was operated in DDA (dataset1) or DIA (dataset 3) mode."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["MS raw files from dataset1 were submitted to MaxQuant software version 2.4.7.0 for protein identification and label-free quantification. Carbamidomethyl (C) was set as a fixed modification and acetyl (protein N-term), carbamyl (N-term) and oxidation (M) were set as variable modifications. First search peptide tolerance of 20 ppm and main search error 10 ppm were used. Trypsin without proline restriction cleavage option was used, with two allowed miscleavages. The minimal unique + razor peptides number was set to 1, and the allowed FDR was 0.01 (1%) for peptide and protein identification. Label-free quantitation was employed with default settings. UniProt database with ‘mouse’ entries was used for the database searches.MS raw files from datasets 2 and  3 were submitted submitted to DIA-NN (version 1.9.2 and 2.3.0) for protein identification and label-free quantification using the library-free function. The UniProt mouse database was used to generate library in silico from a FASTA file. Carbamidomethyl (C) was set as a fixed modification. Trypsin without proline restriction cleavage option was used, with one allowed miscleavage and peptide length range was set to 7-30 amino acids. The mass accuracy was set to 15ppm and precursor false discovery rate (FDR) allowed was 0.01 (1%)."],"omics_type":["Proteomics"],"labhead":["Tuula Nyman"],"instrument_platform":[""],"labhead_affiliation":["Oslo University Hospital"],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"submitter_mail":["maria.stensland@medisin.uio.no"],"publication":["Not available"],"submitter_affiliation":["Oslo University hospital"],"submitter_country":["Norway"],"additional_accession":[]},"is_claimable":false,"name":"Intrinsic errors in mitochondrial translation trigger a decline in cell fitness","description":"Defects in the faithful expression of the human mitochondrial genome underlies disease states, from rare inherited disorders to common pathologies and the aging process itself.  The ensuing decrease in the capacity for oxidative phosphorylation alone cannot account for the phenotype complexity associated with disease.  Here, we address how aberrations in mitochondrial nascent chain synthesis per se exert a decline in cell fitness using a classic model of mitochondrial induced premature aging.  We identify how intrinsic errors during mitochondrial nascent chain synthesis destabilize organelle gene expression, triggering intracellular stress responses that rewire cellular metabolism and cytokine secretion. Further, we show how these mechanisms extend to pathogenic variants associated with inherited human disorders. Together, our findings reveal how aberrations in mitochondrial protein synthesis can sensitize a cell to metabolic challenges associated with disease and pathogen infection independent of oxidative phosphorylation.","dates":{"publication":"2026-10-02","submission":"2025-10-23"},"accession":"PXD069822","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:111205","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:10034","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:1589","NEWT:135622","NEWT:67352","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:383379","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:111225","NEWT:7719","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:1912919","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:44685","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:980415","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:244366","NEWT:1246791","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2709072","NEWT:2853422","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:460523","NEWT:235443","NEWT:1757312","NEWT:85694","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:472","NEWT:940825","NEWT:529507","NEWT:1071661","NEWT:470","NEWT:5911","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:51338","NEWT:575412","NEWT:28112","NEWT:6493","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:8655","NEWT:5147","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:443906","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:38323","NEWT:256318","NEWT:206411","NCBITaxon:6191","NEWT:229533","NEWT:2925","NEWT:214053","NEWT:80863","NEWT:90675","NEWT:52638","NEWT:57075","NEWT:1666905","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:979","NEWT:7370","NEWT:83906","NEWT:1134506","NEWT:255470","NEWT:38783","NEWT:6426","NEWT:33090","NEWT:9935","NEWT:287889","NEWT:305959","NEWT:13489","NEWT:29829","NEWT:92867","NEWT:92866","NCBITaxon:3055","NEWT:51750","NEWT:202950","NEWT:295027","NCBITaxon:11320","NEWT:632957","NEWT:9925","NCBITaxon:9606","NEWT:90690","NEWT:1436183","NEWT:300273","NEWT:4232","NEWT:416348","NEWT:11298","NEWT:4236","NEWT:7742","NEWT:196627","NEWT:200308","NEWT:242507","NEWT:200302","NEWT:870435","NEWT:9913","NEWT:9915","NEWT:105841","NEWT:2666255","NEWT:999810","NCBITaxon:5693","NEWT:28995","NEWT:1392998","NEWT:380394","NEWT:114796","NEWT:226900","NEWT:1266738","NEWT:231490","NEWT:244704","NEWT:7725","NEWT:9909","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