TY  - JOUR
AU  - Aich, Abhishek
AU  - Boshnakovska, Angela
AU  - Witte, Steffen
AU  - Gall, Tanja
AU  - Unthan-Fechner, Kerstin
AU  - Yousefi, Roya
AU  - Chowdhury, Arpita
AU  - Dahal, Drishan
AU  - Methi, Aditi
AU  - Kaufmann, Svenja
AU  - Silbern, Ivan
AU  - Prochazka, Jan
AU  - Nichtova, Zuzana
AU  - Palkova, Marcela
AU  - Raishbrook, Miles
AU  - Koubkova, Gizela
AU  - Sedlacek, Radislav
AU  - Tröder, Simon E
AU  - Zevnik, Branko
AU  - Riedel, Dietmar
AU  - Michanski, Susann
AU  - Möbius, Wiebke
AU  - Ströbel, Philipp
AU  - Lüchtenborg, Christian
AU  - Giavalisco, Patrick
AU  - Urlaub, Henning
AU  - Fischer, Andre
AU  - Brügger, Britta
AU  - Jakobs, Stefan
AU  - Rehling, Peter
TI  - Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in mouse liver.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2024-01031
SP  - 6914
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Reactive Oxygen Species: metabolism
KW  - Mice
KW  - Liver: metabolism
KW  - Liver: pathology
KW  - Inflammation: metabolism
KW  - Inflammation: genetics
KW  - Inflammation: pathology
KW  - Electron Transport Complex IV: metabolism
KW  - Electron Transport Complex IV: genetics
KW  - Oxidative Phosphorylation
KW  - Mitochondria: metabolism
KW  - Humans
KW  - RNA, Mitochondrial: genetics
KW  - RNA, Mitochondrial: metabolism
KW  - Male
KW  - Mitochondrial Proteins: metabolism
KW  - Mitochondrial Proteins: genetics
KW  - Protein Biosynthesis
KW  - Mice, Inbred C57BL
KW  - DEAD-box RNA Helicases: metabolism
KW  - DEAD-box RNA Helicases: genetics
KW  - Female
KW  - Mutation
KW  - DEAD Box Protein 58
KW  - Membrane Proteins
KW  - Cyclooxygenase 1
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Electron Transport Complex IV (NLM Chemicals)
KW  - Ddx58 protein, mouse (NLM Chemicals)
KW  - RNA, Mitochondrial (NLM Chemicals)
KW  - Ptgs1 protein, mouse (NLM Chemicals)
KW  - Mitochondrial Proteins (NLM Chemicals)
KW  - DEAD-box RNA Helicases (NLM Chemicals)
KW  - DEAD Box Protein 58 (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
KW  - Cyclooxygenase 1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11319346
C6  - pmid:39134548
DO  - DOI:10.1038/s41467-024-51109-y
UR  - https://pub.dzne.de/record/271329
ER  -