Nature Communications (Aug 2024)
Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in mouse liver
- 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
Affiliations
- Abhishek Aich
- Department of Cellular Biochemistry, University Medical Center Göttingen
- Angela Boshnakovska
- Department of Cellular Biochemistry, University Medical Center Göttingen
- Steffen Witte
- Department of Cellular Biochemistry, University Medical Center Göttingen
- Tanja Gall
- Department of Cellular Biochemistry, University Medical Center Göttingen
- Kerstin Unthan-Fechner
- Department of Molecular Biochemistry, University Medical Center Göttingen
- Roya Yousefi
- Department of Cellular Biochemistry, University Medical Center Göttingen
- Arpita Chowdhury
- Department of Cellular Biochemistry, University Medical Center Göttingen
- Drishan Dahal
- Department of Cellular Biochemistry, University Medical Center Göttingen
- Aditi Methi
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen
- Svenja Kaufmann
- Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences
- Ivan Silbern
- Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences
- Jan Prochazka
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the CAS, v.v.i, 252 50
- Zuzana Nichtova
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the CAS, v.v.i, 252 50
- Marcela Palkova
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the CAS, v.v.i, 252 50
- Miles Raishbrook
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the CAS, v.v.i, 252 50
- Gizela Koubkova
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the CAS, v.v.i, 252 50
- Radislav Sedlacek
- Czech Centre for Phenogenomics, Institute of Molecular Genetics of the CAS, v.v.i, 252 50
- Simon E. Tröder
- Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne
- Branko Zevnik
- Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne
- Dietmar Riedel
- Laboratory for Electron Microscopy, Max Planck Institute for Multidisciplinary Sciences
- Susann Michanski
- Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen
- Wiebke Möbius
- Max Planck Institute for Multidisciplinary Science, Department of Neurogenetics
- Philipp Ströbel
- Institute of Pathology, University Medical Center Göttingen
- Christian Lüchtenborg
- Heidelberg University Biochemistry Center (BZH)
- Patrick Giavalisco
- Max Planck Institute for Biology of Ageing
- Henning Urlaub
- Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen
- Andre Fischer
- Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen
- Britta Brügger
- Heidelberg University Biochemistry Center (BZH)
- Stefan Jakobs
- Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen
- Peter Rehling
- Department of Cellular Biochemistry, University Medical Center Göttingen
- DOI
- https://doi.org/10.1038/s41467-024-51109-y
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 20
Abstract
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.
