Journal Article

DZNE-2024-01031

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in mouse liver.

Aich, A. ; Boshnakovska, A. ; Witte, S. ; Gall, T. ; Unthan-Fechner, K. ; Yousefi, R. ; Chowdhury, A. ; Dahal, D. ; Methi, A.DZNE* ; Kaufmann, S. ; Silbern, I. ; Prochazka, J. ; Nichtova, Z. ; Palkova, M. ; Raishbrook, M. ; Koubkova, G. ; Sedlacek, R. ; Tröder, S. E. ; Zevnik, B. ; Riedel, D. ; Michanski, S. ; Möbius, W. ; Ströbel, P. ; Lüchtenborg, C. ; Giavalisco, P. ; Urlaub, H. ; Fischer, A.DZNE* ; Brügger, B. ; Jakobs, S. ; Rehling, P.

2024
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-024-51109-y

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.

Keyword(s): Animals (MeSH) ; Reactive Oxygen Species: metabolism (MeSH) ; Mice (MeSH) ; Liver: metabolism (MeSH) ; Liver: pathology (MeSH) ; Inflammation: metabolism (MeSH) ; Inflammation: genetics (MeSH) ; Inflammation: pathology (MeSH) ; Electron Transport Complex IV: metabolism (MeSH) ; Electron Transport Complex IV: genetics (MeSH) ; Oxidative Phosphorylation (MeSH) ; Mitochondria: metabolism (MeSH) ; Humans (MeSH) ; RNA, Mitochondrial: genetics (MeSH) ; RNA, Mitochondrial: metabolism (MeSH) ; Male (MeSH) ; Mitochondrial Proteins: metabolism (MeSH) ; Mitochondrial Proteins: genetics (MeSH) ; Protein Biosynthesis (MeSH) ; Mice, Inbred C57BL (MeSH) ; DEAD-box RNA Helicases: metabolism (MeSH) ; DEAD-box RNA Helicases: genetics (MeSH) ; Female (MeSH) ; Mutation (MeSH) ; DEAD Box Protein 58 (MeSH) ; Membrane Proteins (MeSH) ; Cyclooxygenase 1 (MeSH) ; Reactive Oxygen Species ; Electron Transport Complex IV ; Ddx58 protein, mouse ; RNA, Mitochondrial ; Ptgs1 protein, mouse ; Mitochondrial Proteins ; DEAD-box RNA Helicases ; DEAD Box Protein 58 ; Membrane Proteins ; Cyclooxygenase 1

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Aich, A. ; Patrick, G. ; Rehling, P. ; Aich, A. (Data Collector) ; Boshnakovska, A. (Data Collector) ; Witte, S. (Data Collector) ; Gall, T. (Data Collector) ; Unthan-Fechner, K. (Data Collector) ; Yousefi, R. (Data Collector) ; Chowdhury, A. (Data Collector) ; Dahal, D. (Data Collector) ; Methi, A. (Data Collector)DZNE* ; Kaufmann, S. (Data Collector) ; Silbern, I. (Data Collector) ; Prochazka, J. (Data Collector) ; Nichtova, Z. (Data Collector) ; Palkova, M. (Data Collector) ; Raishbrook, M. (Data Collector) ; Koublova, G. (Data Collector) ; Sedlacek, R. (Data Collector) ; Tröder, S. E. (Data Collector) ; Zevnik, B. (Data Collector) ; Riedel, D. (Data Collector) ; Michanski, S. (Data Collector) ; Möbius, W. (Data Collector) ; Ströbel, P. (Data Collector) ; Lüchtenborg, C. (Data Collector) ; Giavalisco, P. (Data Collector) ; Urlaub, H. (Data Collector) ; Fischer, A. (Data Collector)Extern* ; Brügger, B. (Data Collector) ; Jakobs, S. (Data Collector) ; Rehling, P. (Contact Person)
Dataset: Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in liver
Zenodo (2024) [10.5281/zenodo.10640935]2024 BibTeX | EndNote: XML, Text | RIS

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