Update Advances in Ribosome-associated Quality Control and Ribophagy br

The intracellular protein constantly remains in the dynamic process of synthesis and degradation,andits homeostasis appears to be closely related to the cellular function.A variety of protein quality control(PQC)mechanisms exist to monitor abnormalities occurred during protein synthesis and degradation,thereby ensuringproteome integrity and cellular fitness.The ribosome is the most abundant organelle in cells,and it is the majorsite for protein synthesis,for which each stage from biosynthesis to degradation is tightly controlled by variousquality control mechanisms.Ribosome-associated quality control(RQC)and ribophagy are identified as twomajor ribosome-associated PQC mechanisms that synergistically involve in the maintenance of translationalfunction and protein homeostasis.Also,they represent key players in adjusting ribosome content and translationalactivity for the changing environment,in turn facilitating cell survival under stress conditions.The dysregulationof RQC and ribophagy malfunction can substantially alter cellular fate and render cell death,resulting in the onsetand development of various ribosomopathies,including congenital diseases,neurological diseases,and malignanttumors.Targeting ribosomal dysfunction by restoring effective ribosome-associated PQC may serve as potentialremedy in treating ribosomopathies.The current review focuses on ribosomal-associated PQC with in-depthdiscussion regarding to the key roles of these pathways for the maintenance of protein homeostasis as well as theirpotential effects on the development of various human diseases.