Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System
Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System
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DOI：
10.1016/j.molcel.2018.11.009
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发表时间：
2019-01-17
期刊：
影响因子：
16
通讯作者：
Sun, Woong
中科院分区：
文献类型：
--
作者：
Cho, Hyo Min;Ryu, Jae Ryun;Sun, Woong
线粒体自噬是一种用于消除功能失调的线粒体的线粒体质量控制过程，可以通过动力蛋白相关蛋白1（Drp 1）对线粒体膜电位（MMP）和线粒体分裂的降低的响应来诱导。然而，MMP和线粒体分裂之间的协调选择线粒体网络的受损部分是不太了解。在这里，我们发现，MMP是减少局灶性在裂变位点的Drp 1招聘，这是由Drp 1与线粒体锌转运蛋白Zip 1和Zn 2+进入通过Zip 1-MCU复合物的相互作用启动。分裂后，健康的线粒体恢复MMP水平并再次参与融合-分裂循环，但不能恢复MMP的线粒体经历线粒体自噬。因此，干扰Drp 1和Zip 1之间的相互作用阻断了MMP的减少和随后对受损线粒体的线粒体吞噬选择。这些结果表明，依赖Drp 1的裂变为消除线粒体网络中的“坏扇区”提供了选择性压力，作为线粒体质量监测系统。
Mitophagy, a mitochondrial quality control process for eliminating dysfunctional mitochondria, can be induced by a response of dynamin-related protein 1 (Drp1) to a reduction in mitochondrial membrane potential (MMP) and mitochondrial division. However, the coordination between MMP and mitochondrial division for selecting the damaged portion of the mitochondrial network is less understood. Here, we found that MMP is reduced focally at a fission site by the Drp1 recruitment, which is initiated by the interaction of Drp1 with mitochondrial zinc transporter Zip1 and Zn2+ entry through the Zip1-MCU complex. After division, healthy mitochondria restore MMPlevels and participate in the fusion-fission cycle again, but mitochondria that fail to restore MMP undergo mitophagy. Thus, interfering with the interaction between Drp1 and Zip1 blocks the reduction of MMP and the subsequent mitophagic selection of damaged mitochondria. These results suggest that Drp1-dependent fission provides selective pressure for eliminating "bad sectors'' in the mitochondrial network, serving as a mitochondrial quality surveillance system.