Cologne, North Rhine-Westphalia, Germany
The ubiquitin/proteasome system (UPS) is a major proteolytic route functioning in a cellular network that helps to maintain the proteome during stress and aging. Degradation of damaged proteins is mediated by the 26S proteasome upon attachment of ubiquitin proteins. Another proteolytic system supporting proteostasis is the autophagy-lysosome pathway that degrades proteins inside activated autophagosomes. An age-related impairment of either of these systems causes enhanced protein aggregation and affects lifespan, suggesting functional overlap and cooperation between UPS and autophagy in stress and aging. Despite the progress made in searching for key substrates that are destined for degradation, the major challenge in the field is to understand how these proteolytic systems are mechanistically coordinated to overcome age-related proteotoxicity. The ultimate goal of Thorsten Hoppe’s current research is to assemble a global picture of stress-induced proteolytic networks critical for aging of multicellular organisms. Complementary projects in his group are addressing both cellular and tissue-specific regulation of protein degradation pathways using the powerful genetic model of Caenorhabditis elegans.