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Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System.
Hyo Min Cho1, Jae Ryun Ryu1, Youhwa Jo1
1Department of Anatomy, Korea University College of Medicine, Brain Korea 21 plus, Seoul 02841, Republic of Korea.
Molecular Cell
|December 25, 2018
Summary
Dynamin-related protein 1 (Drp1) initiates mitophagy by targeting damaged mitochondrial sectors. This process involves Drp1 interacting with Zip1, reducing mitochondrial membrane potential (MMP) at fission sites to eliminate dysfunctional mitochondria.
Area of Science:
- Cell Biology
- Mitochondrial Dynamics
- Quality Control
Background:
- Mitophagy eliminates dysfunctional mitochondria via dynamin-related protein 1 (Drp1) in response to reduced mitochondrial membrane potential (MMP) and mitochondrial division.
- The precise coordination between MMP and mitochondrial division in selecting damaged mitochondrial portions remains unclear.
Purpose of the Study:
- To elucidate the coordination between MMP and mitochondrial division in the selective elimination of damaged mitochondria.
- To investigate the role of Drp1, Zip1, and Zn2+ in mitophagy initiation.
Main Methods:
- Investigated Drp1 recruitment and its interaction with Zip1.
- Analyzed Zn2+ influx through the Zip1-MCU complex.
- Observed MMP restoration in healthy mitochondria post-division.
- Examined the effects of interfering with Drp1-Zip1 interaction on mitophagy.
Main Results:
- MMP reduction occurs focally at fission sites, mediated by Drp1 recruitment initiated by Zip1 interaction and Zn2+ entry.
- Healthy mitochondria restore MMP and rejoin the fusion-fission cycle post-division.
- Mitochondria failing to restore MMP undergo mitophagy.
- Inhibiting Drp1-Zip1 interaction prevents MMP reduction and subsequent mitophagy.
Conclusions:
- Drp1-dependent mitochondrial fission acts as a quality surveillance system, selectively eliminating damaged mitochondrial sectors.
- The Drp1-Zip1-Zn2+ axis is crucial for initiating mitophagy by targeting mitochondria with reduced MMP.
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