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Mitochondrial translational regulation coupled to respiratory chain assembly and protein import

Final Report Summary - MITRAC (Mitochondrial translational regulation coupled to respiratory chain assembly and protein import)

The mitochondrial oxidative phosphorylation system assembles from subunits of dual genetic origin. The question as to how the assembly process is regulated and most importantly how the supply of subunits derived from cytosolic and mitochondrial translation are adjusted against each other represents a central challenge in molecular biology with far reaching implications for biomedical research.
In this project we dissected early stages of the assembly process of the respiratory chain complex IV and I to answer the long standing question if a link between biogenesis pathways and translation on mitochondrial ribosomes exists in human mitochondria. Our analyses have identified novel factors that participate in assembly of the complexes and that when defective cause mitochondrial disorders in human. These analyses provide us with a molecular understanding of how the complexes of the respiratory chain assemble in an assisted manner from individual subunits. Moreover, our analyses revealed that in fact mitochondrial translation adapts to the influx of nuclear-encoded subunits. A stalled ribosome nascent chain complex translating COX1 is activated through nuclear-encoded subunits to progress in the translation process. Accordingly, the translation process responds to the availability of nuclear-encoded subunits in a transcript-specific manner.