相分离组织自噬体形成
2020-02-10   阅读:476   来源:自然

日本微生物化学研究所Nobuo N. Noda团队研究发现相分离组织自噬体的形成。该研究202025日发表于国际学术期刊《自然》上。

他们表明自噬体前结构(PAS)实际上是Atg蛋白的液体状聚集物。自噬引发的Atg1复合物在体外经历相分离以形成液滴,抑制相分离的点突变或磷酸化会削弱体内PAS的形成。体外实验表明,Atg1复合物液滴可通过特定的蛋白质-蛋白质相互作用而被束缚在膜上,从而解释了PAS在体内的液泡膜定位。他们提出,相分离在自噬中起着至关重要的促进作用,由此它可以在PAS上组织自噬机器。

据了解,许多生物分子经历液相-液相分离,形成类似液体的聚集物,介导多种细胞功能。自噬可能是利用自噬体降解这种聚集物,自噬体是酵母在自噬体前结构(PAS)中从头合成的双层膜结构。尽管已经鉴定了与PAS相关的Atg蛋白,但由于PAS的体积小且易碎,其理化和功能特性尚不清楚。

附:英文原文

Title: Phase separation organizes the site of autophagosome formation

Author: Yuko Fujioka, Jahangir Md. Alam, Daisuke Noshiro, Kazunari Mouri, Toshio Ando, Yasushi Okada, Alexander I. May, Roland L. Knorr, Kuninori Suzuki, Yoshinori Ohsumi, Nobuo N. Noda

Issue&Volume: 2020-02-05

Abstract: Many biomolecules undergo liquid–liquid phase separation to form liquid-like condensates that mediate diverse cellular functions1,2. Autophagy is able to degrade such condensates using autophagosomes—double-membrane structures that are synthesized de novo at the pre-autophagosomal structure (PAS) in yeast3,4,5. Whereas Atg proteins that associate with the PAS have been characterized, the physicochemical and functional properties of the PAS remain unclear owing to its small size and fragility. Here we show that the PAS is in fact a liquid-like condensate of Atg proteins. The autophagy-initiating Atg1 complex undergoes phase separation to form liquid droplets in vitro, and point mutations or phosphorylation that inhibit phase separation impair PAS formation in vivo. In vitro experiments show that Atg1-complex droplets can be tethered to membranes via specific protein–protein interactions, explaining the vacuolar membrane localization of the PAS in vivo. We propose that phase separation has a critical, active role in autophagy, whereby it organizes the autophagy machinery at the PAS.

DOI: 10.1038/s41586-020-1977-6

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