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Molecular Mechanism of Regulating Autophagy by Liquid-Liquid Phase Separation Revealed

October 25, 2021      Author: Zhang Qing

Recently, Prof. Xue Hongwei's team from School of Agriculture and Biology, Shanghai Jiao Tong University, had their short communication titled "Arabidopsis AUTOPHAGY-RELATED3 (ATG3) facilitates the liquid-liquid phase separation of ATG8e to promote autophagy" published in Science Bulletin. The team's finding that ATG3, an Arabidopsis autophagy-related protein, promotes autophagy by enhancing the liquid-liquid phase separation (LLPS) of ATG8e provides new insights for further research on the regulation mechanism of autophagy.

Through systematic cytological observation, it was found that pseudo-south ATG8e could undergo phase separation in vivo and in vitro. The intrinsically disordered regions (IDR) at the n-terminal participate in the formation of phase separation. Treatment with phase separation inhibitors and observation of genetic materials showed that LLPS of ATG8e played an important role in autophagy. Further research demonstrated that autophagy-related protein ATG3 enhanced the phase separation of ATG8e. And genetic analysis showed that the accumulation of autophagic bodies was lower in the atg8e mutant than in the wild type, indicating that ATG3 affected the LLPS of ATG8e and then regulated autophagy.

Interestingly, the n-terminal regions of ATG8e homologous proteins Atg8 and LC3 in yeast and mammals are also IDR, suggesting that there may be phase separation between mammalian LC3 and yeast Atg8, and the phase separation also participates in autophagy regulation of mammalian cells.

Overall, this study elucidated that autophagy is regulated through the enhancement of liquid-liquid phase separation of ATG8e in Arabidopsis thaliana, specified the important role of ATG3 in the enhancement process, and revealed the existence and physiological significance of phase separation in autophagy. The findings shed lights on further discussion on autophagy biogenesis and the molecular mechanism of regulating autophagy.

 

Paper Link: https://www.sciencedirect.com/science/article/pii/S2095927321006526

 

Keywords

phase separation; AUTOPHAGY-RELATED (ATG); autophagy; ATG3; ATG8e

 

In each cell, various components/organelles (including membranous and non-membranous organelles) assemble at the proper time and space to function. How organelles lacking a membrane form and the physicochemical natures of such organelles remain unknown. Recent studies have shown that membrane-free structures can assemble by liquid-liquid phase separation (LLPS), an essential process in which protein molecules condense into a closed liquid compartment with other proteins or RNAs after they reach a critical threshold concentration.

 

Author: School of Agriculture and Biology, SJTU

Source: School of Agriculture and Biology, SJTU

 Translated by Zhou Rong

 Proofread by Xiao Yangning