Selective Autophagy of the Protein Homeostasis Machinery: Ribophagy, Proteaphagy and ER-Phagy

Abstract

The eukaryotic cell has developed intricate machineries that monitor and maintain proteome homeostasis in order to ensure cellular functionality. This involves the carefully coordinated balance between protein synthesis and degradation pathways, which are dynamically regulated in order to meet the constantly changing demands of the cell. Ribosomes, together with the endoplasmic reticulum (ER), are the key drivers of protein synthesis, folding, maturation and sorting, while the proteasome plays a pivotal role in terminating the existence of thousands of proteins that are misfolded, damaged or otherwise obsolete. The synthesis, structure and function of these dedicated machines has been studied for decades, however, much less is understood about the mechanisms that control and execute their own turnover. Autophagy, an evolutionarily conserved catabolic pathway, mediates degradation of a large variety of cytosolic substrates, ranging from single proteins to entire organelles or multisubunit macromolecular complexes. In this review, we focus on selective autophagy of three key components of the protein homeostasis machinery: ribosomes, ER and proteasomes, through the selective autophagy pathways of ribophagy, ER-phagy, and proteaphagy. We discuss newly discovered mechanisms for the selective clearance of these substrates, which are often stress-dependent and involve specialized signals for cargo recognition by a growing number of receptors. We further discuss the interplay between these pathways and their biological impact on key aspects of proteome homeostasis and cellular function in health and disease.

Selective autophagy of intracellular organelles: Recent research advances

“…Disruption of Snx4 localization also compromises proteaphagy 206 . Interestingly, Snx4 is required for both proteaphagy and ribophagy, and Ubp3 is the common regulator of both proteaphagy and ribophagy 206 - 208 . In contrast, during carbon starvation, proteasomes are reversibly sorted to avoid autophagic degradation.…”

The Existence and Localization of Nuclear snoRNAs in Arabidopsis thaliana Revisited

“…Most of the processes occur in the nucleolus, a specialized membrane-less compartment of the nucleus [ 7 , 8 , 9 , 10 , 11 ]. Consistent with the importance of functional ribosomes, many diseases are related to failures in ribosomal assembly [ 12 , 13 , 14 , 15 ], and therefore, cellular mechanisms for quality control of ribosome assembly have evolved [ 16 , 17 , 18 ]. Ribosome biogenesis is regulated by many ribosome biogenesis factors (RBFs [ 1 , 2 , 3 , 4 , 5 , 6 ]) and small nucleolar RNAs (snoRNAs), usually components of ribonucleolar particles named snoRNPs [ 19 ].…”

BoxCarmax: a high-selectivity data-independent acquisition mass spectrometry method for the analysis of protein turnover and complex samples

“…However, the impact of serum starvation on cellular proteome and proteostasis remains unclear 42, 43 . The major cellular degradative mechanisms during nutritional deprivation present one of the most fundamental questions in cell biology [39][40][41]44 . Figure 4C illustrated that BoxCarmax improved the overall quantification accuracy in pSILAC experiment especially on early time points, which are essential for robust and accurate protein turnover calculation 24,26 .…”