Yoshii Saori R, Mizushima Noboru
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Biochim Biophys Acta. 2015 Oct;1853(10 Pt B):2797-801. doi: 10.1016/j.bbamcr.2015.01.013. Epub 2015 Jan 26.
Autophagy is an intracellular catabolic system that degrades cytoplasmic proteins and organelles. Damaged mitochondria can be degraded by a selective type of autophagy, which is termed mitophagy. PINK1-Parkin-dependent mitophagy has been extensively studied in the mammalian system. PINK1 accumulates on damaged mitochondria to recruit Parkin, which subsequently ubiquitinates a broad range of outer mitochondrial membrane proteins. Ubiquitinated mitochondria associate with the autophagosome formation site, and are selectively incorporated into autophagosomes. During this process, damaged mitochondria first associate with the autophagosome formation site together with upstream autophagy factors, then are efficiently incorporated into autophagosomes through binding with autophagosome adaptors. This "two-step model" may be applied to other selective types of autophagy.
自噬是一种细胞内分解代谢系统，可降解细胞质蛋白和细胞器。受损的线粒体可通过一种选择性自噬类型被降解，这种自噬被称为线粒体自噬。在哺乳动物系统中，PINK1 - Parkin依赖性线粒体自噬已得到广泛研究。PINK1在受损线粒体上积累以招募Parkin，随后Parkin使广泛的线粒体外膜蛋白泛素化。泛素化的线粒体与自噬体形成位点相关联，并被选择性地纳入自噬体。在此过程中，受损线粒体首先与自噬体形成位点以及上游自噬因子一起结合，然后通过与自噬体衔接蛋白结合而有效地纳入自噬体。这种“两步模型”可能适用于其他选择性自噬类型。
