Molecular Basis of Mitochondrial Diseases Exemplified by Mutation of the Translation Factor Cox14

by Steffen Witte
Doctoral thesis
Date of Examination:2023-11-16
Date of issue:2023-11-07
Advisor:Prof. Dr. Peter Rehling
Referee:Prof. Dr. Dörthe Katschinski
Referee:Prof. Dr. Thomas Meyer
Persistent Address: http://dx.doi.org/10.53846/goediss-10162

 

 

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Abstract

English

Mitochondrial oxidative phosphorylation (OXPHOS) fuels cellular ATP demands. OXPHOS defects lead to severe human disorders with unexplained tissue specific pathologies. More and more evidence shows that mitochondrial dysfunction is an important pathomechanism in the development of many common human diseases. 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. In this study, a COX14 mouse mutant corresponding to a patient with complex IV deficiency was generated. COX14M19I mice display broad tissue-specific pathologies. A hallmark phenotype is severe liver inflammation linked to release of mitochondrial nucleic acids into the cytosol triggering inflammation via interferon type I activation. Our study provides mechanistic insight into how defective mitochondrial gene expression causes tissue-specific inflammation.
Keywords: Mitochondria; Mitochondrial Dysfunction
 
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