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Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00156

Emerging role of the nucleolar stress response in autophagy

  • 1Ulm University Medical Center, Germany
  • 2Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Ulm, Germany

Autophagy represents a conserved self-digestion program, which allows regulated degradation of cellular material. Autophagy is activated by cellular stress, serum starvation and nutrient deprivation. Several autophagic pathways have been uncovered, which either non-selectively or selectively target the cellular cargo for lysosomal degradation. Autophagy engages the coordinated action of various key regulators involved in the steps of autophagosome formation, cargo targeting and lysosomal fusion. While non-selective (macro)autophagy is required for removal of bulk material or recycling of nutrients, selective autophagy mediates specific targeting of damaged organelles or protein aggregates. By proper action of the autophagic machinery, cellular homeostasis is maintained. In contrast, failure of this fundamental process is accompanied by severe pathophysiological conditions. Hallmarks of neuropathological disorders are for instance accumulated, mis-folded protein aggregates and damaged mitochondria. The nucleolus has been recognized as central hub in the cellular stress response. It represents a sub-nuclear organelle essential for ribosome biogenesis and also functions as stress sensor by mediating cell cycle arrest or apoptosis. Thus, proper nucleolar function is mandatory for cell growth and survival. Here, we highlight the emerging role of nucleolar factors in the regulation of autophagy. Moreover, we discuss the nucleolar stress response as a novel signaling pathway in the context of autophagy, health and disease.

Keywords: Ribosome biogenesis, nucleoli, nucleolar stress response, Autophagy, Neuron, aggregates, Mitochondria, rRNA processing, mitophagy, Aggrephagy

Received: 21 Dec 2018; Accepted: 08 Apr 2019.

Edited by:

Kerry L. Tucker, University of New England, United States

Reviewed by:

Grzegorz Kreiner, Institute of Pharmacology, Polish Academy of Sciences, Poland
Cláudia Pereira, Faculty of Medicine, University of Coimbra, Portugal  

Copyright: © 2019 Pfister. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Astrid S. Pfister, Ulm University Medical Center, Ulm, Germany,