Abstract of the article Mitochondrial oxidative phosphorylation (OXPHOS) fuels cellular ATP demands. OXPHOS defects lead to severe human disorders with unexplained tissue specific pathologies. Mitochondrial gene expression is essential for OXPHOS biogenesis since core subunits of the complexes are mitochondrial-encoded. COX14 is required for translation of COX1, the central mitochondrial-encoded subunit of complex IV. Here we generated a COX14 mutant mouse corresponding to a patient with complex IV deficiency. COX14M19I mice display broad tissue-specific pathologies. A hallmark phenotype is severe liver inflammation linked to release of mitochondrial RNA into the cytosol sensed by RIG-1 pathway. We find that mitochondrial RNA release is triggered by increased reactive oxygen species production in the deficiency of complex IV. Additionally, we generated a COA3Y72C mouse, affected in an assembly factor in early COX1 biogenesis, which displayed a similar yet milder inflammatory phenotype. Our study provides mechanistic insight into how defective mitochondrial gene expression causes tissue-specific inflammation.

Data Content In this data repository Ultra High-Performance Chromatography (UPLC) and Ion Chromatography (IC)- high resolution mass spectrometry (HRMS) metabolomic data is provided. The data consists of all analyzed raw files and the associated peak picking files (TraceFinder 5.1, Thermo Fisher Scientific). The data with the abreviation "Bz_QE_Plus" contains the UPLC-MS data of bezoylchloride derivatized amines, phenols, thiols, and some alcohols measured on a Q-Exactive Plus mass spectrometer), while the files with the abbreviation "IC_HF_TF" contain the anion chromatographic data measured on a Q-Exactive Plus coupled to an Integrion ion chroatograph. The provided data is associated to an article submitted to Nature Communications (“Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in liver”), describing the analysis of COX14 and COA3 mutants (see abstract below). The sample and data analysis section, which is also provided in the supplementary section of the above mentioned article, are also attached as, doc files to the deposited data.