德国歌德大学Ivan Dikic和Christian Pohl研究团队合作阐述了泛素-蛋白酶体系统如何调控自噬和细胞质量控制。这一研究成果发表在2019年11月15日出版的国际学术期刊《科学》上。

研究人员讨论了真核细胞中负责蛋白质和细胞器降解的两个主要质量控制系统，泛素-蛋白酶体系统（UPS）和自噬的重要性。UPS和自噬形成了一个相互联系的质量控制网络，在该网络中，决定性因素是生物物理参数（结合亲和力、局部浓度以及亲和力）和分区（通过膜、液-液相分离或聚合）。研究人员重点介绍了细胞质量控制因素，这些因素揭示了它们如何向大分子复合、液-液相分离的亚细胞结构或膜结合细胞器的不同部署。最后，研究人员强调需要不断深入定量和机理研究，以了解UPS和自噬在人类病理生理学中的作用。

研究人员表示，为了达到稳态，细胞进化出动态的、自我调节的质量控制过程，以适应新的环境条件并防止长时间的破坏。

附：英文原文

Title: Cellular quality control by the ubiquitin-proteasome system and autophagy

Author: Christian Pohl, Ivan Dikic

Issue&Volume: 2019/11/15

Abstract: To achieve homeostasis, cells evolved dynamic and self-regulating quality control processes to adapt to new environmental conditions and to prevent prolonged damage. We discuss the importance of two major quality control systems responsible for degradation of proteins and organelles in eukaryotic cells: the ubiquitin-proteasome system (UPS) and autophagy. The UPS and autophagy form an interconnected quality control network where decision-making is self-organized on the basis of biophysical parameters (binding affinities, local concentrations, and avidity) and compartmentalization (through membranes, liquid-liquid phase separation, or the formation of aggregates). We highlight cellular quality control factors that delineate their differential deployment toward macromolecular complexes, liquid-liquid phase-separated subcellular structures, or membrane-bound organelles. Finally, we emphasize the need for continuous promotion of quantitative and mechanistic research into the roles of the UPS and autophagy in human pathophysiology.

DOI: 10.1126/science.aax3769

Source: https://science.sciencemag.org/content/366/6467/818