Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System

Mol Cell. 2019 Jan 17;73(2):364-376.e8. doi: 10.1016/j.molcel.2018.11.009. Epub 2018 Dec 20.


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.

Keywords: Drp1; Zip1; mitochondrial fission; mitochondrial membrane potential; mitochondrial quality control; mitochondrial quality surveillance; mitophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Dynamins
  • Energy Metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Membrane Potential, Mitochondrial
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Dynamics*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Mitophagy*
  • Mutation
  • Neurons / metabolism
  • Neurons / pathology
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Time Factors
  • Zinc / metabolism


  • Calcium Channels
  • Cation Transport Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • SLC39A1 protein, human
  • mitochondrial calcium uniporter
  • Adenosine Triphosphate
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dynamins
  • Zinc