核糖体相关质量控制与核糖体自噬研究进展

细胞中蛋白质处于不断合成和降解的动态更新过程中，其稳态与细胞功能密切相关。细胞中存在多种蛋白质质量控制（protein quality control，PQC）机制来监测蛋白质合成和降解过程的异常，以确保蛋白质组的完整性和细胞适应性。核糖体是细胞内数量最多的细胞器，系细胞内蛋白质合成的主要场所。现已明确，核糖体相关质量控制（ribosome-associated quality control，RQC）与核糖体自噬能通过溶酶体依赖和非依赖途径调节细胞内核糖体数量及功能以维持蛋白质稳态，从而增强细胞在应激状态下的适应能力。RQC失调、核糖体自噬障碍则参与多种疾病的发生及发展过程，靶向RQC和核糖体自噬可能成为防治多种疾病的有效手段。本综述聚焦核糖体相关的PQC途径，并进一步讨论了它们在蛋白质稳态维持中的重要地位及其在人类疾病发生发展中的潜在作用。

Update Advances in Ribosome-associated Quality Control and Ribophagy

The intracellular protein constantly remains in the dynamic process of synthesis and degradation, and its 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 ensuring proteome integrity and cellular fitness. The ribosome is the most abundant organelle in cells, and it is the major site for protein synthesis, for which each stage from biosynthesis to degradation is tightly controlled by various quality control mechanisms. Ribosome-associated quality control (RQC) and ribophagy are identified as two major ribosome-associated PQC mechanisms that synergistically involve in the maintenance of translational function and protein homeostasis. Also, they represent key players in adjusting ribosome content and translational activity for the changing environment, in turn facilitating cell survival under stress conditions. The dysregulation of RQC and ribophagy malfunction can substantially alter cellular fate and render cell death, resulting in the onset and development of various ribosomopathies, including congenital diseases, neurological diseases, and malignant tumors. Targeting ribosomal dysfunction by restoring effective ribosome-associated PQC may serve as potential remedy in treating ribosomopathies. The current review focuses on ribosomal-associated PQC with in-depth discussion regarding to the key roles of these pathways for the maintenance of protein homeostasis as well as their potential effects on the development of various human diseases.