Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System

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. [Display omitted] •Drp1 reduces MMP via interaction with mitochondrial Zn2+ transporter Zip1•Drp1-Zip1 interaction promotes the elimination of bad mitochondrial parts by mitophagy•Drp1-dependent MMP reduction is for the selective removal of dysfunctional mitochondria Cho et al. report that Drp1 that is the executioner for mitochondrial fission can reduce the mitochondrial membrane potential (MMP) during the mitochondrial division, and this new action helps identify bad sectors in the interconnected mitochondria.