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Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System

2018; Elsevier BV; Volume: 73; Issue: 2 Linguagem: Inglês

10.1016/j.molcel.2018.11.009

1097-4164

Hyo Min Cho, Jae Ryun Ryu, Youhwa Jo, Tae Woong Seo, Ye Na Choi, June Hoan Kim, Jee Min Chung, Bongki Cho, Ho Chul Kang, Seong-Woon Yu, Soon Ji Yoo, Hyun Kim, Woong Sun,

Metabolism and Genetic Disorders

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 MMP levels 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.