| Autor: |
Abhishek Aich, Angela Boshnakovska, Steffen Witte, Tanja Gall, Kerstin Unthan-Fechner, Roya Yousefi, Arpita Chowdhury, Drishan Dahal, Aditi Methi, Svenja Kaufmann, Ivan Silbern, Jan Prochazka, Zuzana Nichtova, Marcela Palkova, Miles Raishbrook, Gizela Koubkova, Radislav Sedlacek, Simon E. Tröder, Branko Zevnik, Dietmar Riedel, Susann Michanski, Wiebke Möbius, Philipp Ströbel, Christian Lüchtenborg, Patrick Giavalisco, Henning Urlaub, Andre Fischer, Britta Brügger, Stefan Jakobs, Peter Rehling |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-20 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-51109-y |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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