Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor.
Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor.
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DOI：
10.1016/j.cell.2016.11.042
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发表时间：
2017-01-12
期刊：
影响因子：
64.5
通讯作者：
Levine B
中科院分区：
文献类型：
--
作者：
Wei Y;Chiang WC;Sumpter R Jr;Mishra P;Levine B
通过自噬去除不需要的或受损的线粒体，这一过程称为线粒体自噬，对于发育、细胞稳态、肿瘤抑制以及预防神经退行性变和衰老中的关键事件至关重要。然而，线粒体自噬的确切机制仍然不确定。在这里，我们确定了线粒体内膜蛋白，抑制素2（PHB2），作为一个重要的线粒体自噬受体参与靶向线粒体自噬降解。在线粒体去极化和蛋白酶体依赖性外膜破裂后，PHB2通过LC 3相互作用区（LIR）结构域结合自噬体膜相关蛋白LC 3。PHB2是哺乳动物细胞中帕金森诱导的线粒体自噬和C.优雅的。我们的研究结果指出了真核细胞线粒体自噬的保守机制，并证明了抑制素2的功能，可能是其在生理学，衰老和疾病中的作用的基础。
The removal of unwanted or damaged mitochondria by autophagy, a process called mitophagy, is essential for key events in development, cellular homeostasis, tumor suppression, and prevention of neurodegeneration and aging. However, the precise mechanisms of mitophagy remain uncertain. Here, we identify the inner mitochondrial membrane protein, prohibitin 2 (PHB2), as a crucial mitophagy receptor involved in targeting mitochondria for autophagic degradation. PHB2 binds the autophagosomal membrane-associated protein LC3 through an LC3-interaction region (LIR) domain upon mitochondrial depolarization and proteasome-dependent outer membrane rupture. PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans. Our findings pinpoint a conserved mechanism of eukaryotic mitophagy and demonstrate a function of prohibitin 2 that may underlie its roles in physiology, aging, and disease.