Surveillance of nucleolar homeostasis and ribosome maturation by autophagy and the ubiquitin-proteasome system.

• Emerging connection between the nucleolar stress response and autophagy. • Involvement of the ubiquitin-proteasome system (UPS) and autophagy in ribosome biogenesis and protein homeostasis. • Impaired ribosome biogenesis induces nucleolar stress and p53 activation. • Autophagy activation in response to nucleolar stress as a cytoprotective mechanism. The nucleolus functions as the cellular hub for the initiation and early steps of ribosome biogenesis. Ribosomes are key components of the translation machinery and, accordingly, their abundance needs to be adjusted to the cellular energy status. Further, to ensure translational fidelity, the integrity and quality of ribosomes needs to be monitored under conditions of cellular stress. Stressful insults, such as nutrient, genotoxic or proteotoxic stress, interfere with ribosome biogenesis and activate a cellular response referred to as nucleolar stress. This nucleolar stress response typically affects nucleolar integrity and is intricately linked to the activation of protein quality control pathways, including (i) the ubiquitin proteasome system (UPS) and (ii) the autophagy machinery, to restore cellular proteostasis. Here we will review some key features of the nucleolar stress response with a particular focus on the role of the UPS and autophagy in this process. [ABSTRACT FROM AUTHOR]