Phase-separated Condensates in Autophagosome Formation and Autophagy Regulation

Biomacromolecules partition into numerous types of biological condensates or membrane-less organelles via liquid-liquid phase separation (LLPS). Newly formed liquid-like condensates may further undergo phase transition to convert into other material states, such as gel or solid states. Different biological condensates possess distinct material properties to fulfil their physiological functions in diverse cellular pathways and processes. Phase separation and condensates are extensively involved in the autophagy pathway. The autophagosome formation sites in both yeast and multicellular organisms are assembled as phase-separated condensates. TORC1, one of the core regulators of the autophagy-lysosome pathway, is subject to nonconventional regulation by multiple biological condensates. TFEB, the master transcription factor of the autophagy-lysosome pathway, phase separates to assemble liquid-like condensates involved in transcription of autophagic and lysosomal genes. The behaviors and transcriptional activity of TFEB condensates are governed by their material properties, thus suggesting novel autophagy intervention strategies. The phase separation process and the resulting condensates are emerging therapeutic targets for autophagy-related diseases.