Mitochondrial Dysfunction and the Quality Control Network

In our work, we have shown that the mitochondrial proteome consists of more than 1,100 in human cells and 900 high-confidence proteins in the yeast Saccharomyces cerevisiae. Most of these proteins are synthesized at cytosolic ribosomes and thus are imported via different import routes into mitochondria. We identified many new mitochondrial components, including many multiple localized proteins. The ongoing exploration of their functions is a major task to eventually obtain a complete picture of mitochondrial functions. This protein-centric research is important because mitochondrial dysfunction is associated with numerous human diseases and aging processes.

In our current work, we want to understand how human cells respond to mitochondrial dysfunction and how they maintain proteostasis when different mitochondrial protein import pathways are impaired. To reach this aim, we are studying the mitochondria-associated protein quality control network employing modern biochemical and latest functional proteomics methods. Specifically, we want to reveal intracellular signaling mechanisms regulating selective protein synthesis and protein degradation under acute mitochondrial stress conditions.