MITRAC · Mitochondrial translational regulation coupled to respiratory chain assembly and protein import

Mitochondrial respiratory chain complexes assemble from nuclear- and mitochondria-encoded subunits in the inner membrane. To protect cells from accumulating unassembled subunits in the membrane, ROS generation, or damage of mitochondrial integrity, regulatory mechanisms to balance and control the fidelity of the assembly process have evolved, encorporating a retention system enabling the preservation of a select few founding complexes for on-demand assembly. In yeast mitochondria, a feedback mechanism has been identified for the cytochrome oxidase in which assembly-intermediates specifically inactivate translation of the core subunit Cox1. It is controversially debated if similar translation regulating mechanisms exist in human mitochondria. However, our recent findings show that in human mitochondria assembly intermediates of respiratory chain complexes affect translation, nevertheless the underlying sensing and signalling mechanisms as well as the protein components appear to be more complex than in yeast. We aim to understand how this regulatory cycle is established