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@ARTICLE{Aich:271329,
author = {Aich, Abhishek and Boshnakovska, Angela and Witte, Steffen
and Gall, Tanja and Unthan-Fechner, Kerstin and Yousefi,
Roya and Chowdhury, Arpita and Dahal, Drishan and Methi,
Aditi and Kaufmann, Svenja and Silbern, Ivan and Prochazka,
Jan and Nichtova, Zuzana and Palkova, Marcela and
Raishbrook, Miles and Koubkova, Gizela and Sedlacek,
Radislav and Tröder, Simon E and Zevnik, Branko and Riedel,
Dietmar and Michanski, Susann and Möbius, Wiebke and
Ströbel, Philipp and Lüchtenborg, Christian and
Giavalisco, Patrick and Urlaub, Henning and Fischer, Andre
and Brügger, Britta and Jakobs, Stefan and Rehling, Peter},
title = {{D}efective mitochondrial {COX}1 translation due to loss of
{COX}14 function triggers {ROS}-induced inflammation in
mouse liver.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2024-01031},
pages = {6914},
year = {2024},
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.},
keywords = {Animals / Reactive Oxygen Species: metabolism / Mice /
Liver: metabolism / Liver: pathology / Inflammation:
metabolism / Inflammation: genetics / Inflammation:
pathology / Electron Transport Complex IV: metabolism /
Electron Transport Complex IV: genetics / Oxidative
Phosphorylation / Mitochondria: metabolism / Humans / RNA,
Mitochondrial: genetics / RNA, Mitochondrial: metabolism /
Male / Mitochondrial Proteins: metabolism / Mitochondrial
Proteins: genetics / Protein Biosynthesis / Mice, Inbred
C57BL / DEAD-box RNA Helicases: metabolism / DEAD-box RNA
Helicases: genetics / Female / Mutation / DEAD Box Protein
58 / Membrane Proteins / Cyclooxygenase 1 / Reactive Oxygen
Species (NLM Chemicals) / Electron Transport Complex IV (NLM
Chemicals) / Ddx58 protein, mouse (NLM Chemicals) / RNA,
Mitochondrial (NLM Chemicals) / Ptgs1 protein, mouse (NLM
Chemicals) / Mitochondrial Proteins (NLM Chemicals) /
DEAD-box RNA Helicases (NLM Chemicals) / DEAD Box Protein 58
(NLM Chemicals) / Membrane Proteins (NLM Chemicals) /
Cyclooxygenase 1 (NLM Chemicals)},
cin = {AG Fischer},
ddc = {500},
cid = {I:(DE-2719)1410002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11319346},
pubmed = {pmid:39134548},
doi = {10.1038/s41467-024-51109-y},
url = {https://pub.dzne.de/record/271329},
}