Débora B. Trentini Schmidt

Sustaining proteome balance is a challenging task in the face of many external and endogenous stresses that accumulate during ageing. This task is carried out by a large number of intricate cellular pathways promoting correct protein folding and the elimination of defective protein species. Most protein quality control systems act post-translationally, thereby allowing new proteins to engage with the protein folding machinery prior to decisions about degradation. A notable exception is the ribosome-associated quality control (RQC) pathway, which functions in removing partially synthesized protein products from ribosomes that have stalled during translation. In recent years, it became evident that the stalled ribosome serves as a signal for multiple processes, including protein quality control, mRNA silencing and degradation, and stress signaling. Our aim is to elucidate what the physiologically relevant causes of ribosome stalling are, and how RQC failure is connected to loss of proteome homeostasis and neurodegeneration.