Nix is a selective autophagy receptor for mitochondrial clearance
Nix is a selective autophagy receptor for mitochondrial clearance
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DOI：
10.1038/embor.2009.256
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发表时间：
2010-01-01
期刊：
影响因子：
7.7
通讯作者：
Dikic, Ivan
中科院分区：
文献类型：
--
作者：
Novak, Ivana;Kirkin, Vladimir;Dikic, Ivan
自噬是一种细胞内稳态途径，它将大量的细胞质物质输送到溶酶体中进行降解。最近的证据表明，自噬介导了细胞中蛋白质聚集体、细胞器和微生物的选择性清除。然而，针对自噬途径的特定底物的特异性仍然知之甚少。在这里，我们发现线粒体蛋白Nix是一种选择性自噬受体，通过与LC3/GABARAP蛋白结合，而LC3/GABARAP蛋白是自噬体膜生长所需的泛素样修饰剂。在培养细胞中，Nix通过其氨基末端lc3相互作用区将GABARAP-L1招募到受损的线粒体。此外，Nix: LC3/GABARAP相互作用的消融延缓了成熟小鼠网织细胞的线粒体清除。因此，Nix作为一种自噬受体，在线粒体损伤后和红细胞分化过程中介导线粒体清除。
Autophagy is the cellular homeostatic pathway that delivers large cytosolic materials for degradation in the lysosome. Recent evidence indicates that autophagy mediates selective removal of protein aggregates, organelles and microbes in cells. Yet, the specificity in targeting a particular substrate to the autophagy pathway remains poorly understood. Here, we show that the mitochondrial protein Nix is a selective autophagy receptor by binding to LC3/GABARAP proteins, ubiquitin-like modifiers that are required for the growth of autophagosomal membranes. In cultured cells, Nix recruits GABARAP-L1 to damaged mitochondria through its amino-terminal LC3-interacting region. Furthermore, ablation of the Nix: LC3/GABARAP interaction retards mitochondrial clearance in maturing murine reticulocytes. Thus, Nix functions as an autophagy receptor, which mediates mitochondrial clearance after mitochondrial damage and during erythrocyte differentiation.