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 describe 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 describe a COA3Y72C mouse, affected in an assembly factor that cooperates with COX14 in early COX1 biogenesis, which displays a similar yet milder inflammatory phenotype. Our study provides insight into a link between defective mitochondrial gene expression and tissue-specific inflammation.
- MeSH
- cyklooxygenasa 1 * MeSH
- DEAD box protein 58 MeSH
- DEAD-box RNA-helikasy metabolismus genetika MeSH
- játra * metabolismus patologie MeSH
- lidé MeSH
- membránové proteiny MeSH
- mitochondriální proteiny metabolismus genetika MeSH
- mitochondrie metabolismus MeSH
- mutace MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- oxidativní fosforylace * MeSH
- proteosyntéza MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- respirační komplex IV * metabolismus genetika MeSH
- RNA mitochondriální genetika metabolismus MeSH
- zánět * metabolismus genetika patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklooxygenasa 1 * MeSH
- Ddx58 protein, mouse MeSH Prohlížeč
- DEAD box protein 58 MeSH
- DEAD-box RNA-helikasy MeSH
- membránové proteiny MeSH
- mitochondriální proteiny MeSH
- Ptgs1 protein, mouse MeSH Prohlížeč
- reaktivní formy kyslíku * MeSH
- respirační komplex IV * MeSH
- RNA mitochondriální MeSH
