State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China; Shenzhen Research Institute of Xiamen University, Shenzhen, 518057, China.
Department of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Trends Biochem Sci. 2024 Jun;49(6):494-505. doi: 10.1016/j.tibs.2024.03.004. Epub 2024 Apr 1.
Autophagy - a highly regulated intracellular degradation process - is pivotal in maintaining cellular homeostasis. Liquid-liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) family of proteins is best known for its regulatory role in initiating autophagy, but there is growing evidence that the functional spectrum of ULK/Atg1 extends beyond autophagy regulation. In this review, we explore the spatial and temporal regulation of the ULK/Atg1 family of kinases, focusing on their recruitment to LLPS-driven compartments, and highlighting their multifaceted functions beyond their traditional role.
自噬作用——一种高度调控的细胞内降解过程——在维持细胞内稳态方面起着关键作用。液-液相分离(LLPS)是调节无膜隔室形成和功能的基本机制。最近的研究揭示了 LLPS 与自噬之间的联系,表明相分离事件可能协调自噬机制和货物隔离的时空组织。非典型卷曲螺旋激酶 1(UNC-51 样激酶 1)/自噬相关蛋白 1(Atg1)家族的蛋白以其在启动自噬中的调节作用而闻名,但越来越多的证据表明,ULK/Atg1 家族的功能谱超出了自噬调节。在这篇综述中,我们探讨了 ULK/Atg1 家族激酶的时空调节,重点关注它们向 LLPS 驱动隔室的募集,并强调了它们在传统作用之外的多方面功能。