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Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System

Cho, HM; Ryu, JR; Jo, Y; Seo, TW; Choi, YN; Kim, JH; Chung, JM; Cho, B; Kang, HC; Yu, SW; Yoo, SJ; Kim, H; Sun, W
Molecular cell, 73(2). : 364-376.e1-e8, 2019
Journal Title
Molecular cell
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 Zn(2+) 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.
Drp1Zip1mitochondrial fissionmitochondrial membrane potentialmitochondrial quality controlmitochondrial quality surveillancemitophagy
MeSH terms
Adenosine Triphosphate / metabolismAnimalsCalcium Channels / geneticsCalcium Channels / metabolismCation Transport Proteins / geneticsCation Transport Proteins / metabolism*Cerebral Cortex / metabolismCerebral Cortex / pathologyEnergy MetabolismGTP Phosphohydrolases / geneticsGTP Phosphohydrolases / metabolism*HEK293 CellsHeLa CellsHumansMembrane Potential, MitochondrialMicrotubule-Associated Proteins / geneticsMicrotubule-Associated Proteins / metabolism*Mitochondria / geneticsMitochondria / metabolism*Mitochondria / pathologyMitochondrial Dynamics*Mitochondrial Proteins / geneticsMitochondrial Proteins / metabolism*Mitophagy*MutationNeurons / metabolismNeurons / pathologyProtein BindingProtein Interaction Domains and MotifsRats, Sprague-DawleySignal TransductionTime FactorsZinc / metabolism
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
강, 호철
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