粒体自噬
自噬
ATG8型
帕金
细胞生物学
品脱1
泛素
线粒体
膜
化学
生物
生物化学
细胞凋亡
病理
基因
医学
疾病
帕金森病
作者
Zi Yang,Saori R. Yoshii,Yuji Sakai,Haruka Chino,Roland L. Knorr,Noboru Mizushima
标识
DOI:10.1101/2023.09.11.557117
摘要
Abstract During PINK1 and Parkin-mediated mitophagy, autophagy adaptors are recruited to depolarized mitochondria to promote the selective degradation of mitochondria. Autophagy adaptors such as OPTN and NDP52 bridge mitochondria and autophagosomal membranes by binding to ubiquitinated mitochondrial proteins and autophagosomal ATG8 family proteins. Here, we demonstrate that OPTN and NDP52 form sheet-like phase-separated condensates with liquid-like properties on the surface of ubiquitinated mitochondria. The dynamic and liquid-like feature of OPTN condensates is important for mitophagy activity because reducing the liquidity of OPTN–ubiquitin condensates suppresses the recruitment of ATG9 vesicles and impairs mitophagy. Based on these results, we propose a dynamic liquid-like model of autophagy adaptors, in contrast to a stoichiometric model, to explain their interactions between autophagic membranes (i.e., ATG9 vesicles and isolation membranes) and mitochondrial membranes during Parkin-mediated mitophagy. This model underscores the importance of liquid–liquid phase separation in facilitating membrane– membrane contacts, likely through the generation of capillary forces.
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