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Updated: May 9, 2025

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
Published on: May 4, 2016
Retroviral foamy virus gag induces parkin-dependent mitophagy
Shanshan Wang1, Tongtong Du1, Jun Yan2
1Hubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China.
Background:
Prototype foamy virus (PFV) is a complex retrovirus that can maintain latent infection for life after viral infection of the host. However, the mechanism of latent infection with PFV remains unclear. Our previous studies have shown that PFV promotes autophagy flux, but whether PFV causes mitophagy remains unclear.
Results:
In this study, we demonstrated that PFV infection damages mitochondria, increases mitochondria reactive oxygen species (mtROS) production, and induces mitophagy in a time-dependent manner. Further investigation revealed that PFV Gag is a crucial protein responsible for triggering mitophagy. The overexpression of Gag leads to mitochondrial damage and stimulates mitophagy in a dose-dependent manner. Additionally, overexpression of Gag activates the PINK1-Parkin signaling pathway, while the knockdown of Parkin inhibits Gag-induced mitophagy. Furthermore, Rab5a was significantly upregulated in cells overexpressed Gag, and the inhibition of Rab5a reversed the effects of Gag-induced mitophagy.
Conclusions:
Our data suggested that PFV can induce mitophagy and Gag induces Parkin-dependent mitophagy by upregulating Rab5a. These findings not only enhance a better understanding of the foamy virus infection mechanisms but also provide critical insights into novel virus-host cell interactions.
Insights
Prototype foamy virus (PFV) infection triggers mitophagy, a process where cells degrade damaged mitochondria. The viral Gag protein is key, activating the PINK1-Parkin pathway and upregulating Rab5a to promote this process.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Prototype foamy virus (PFV) establishes lifelong latent infections.
- Mechanisms of PFV latent infection are not fully understood.
- PFV is known to promote autophagy, but its role in mitophagy is unclear.
Purpose of the Study:
- To investigate whether PFV infection induces mitophagy.
- To identify viral factors responsible for mitophagy induction.
- To elucidate the molecular pathways involved in PFV-induced mitophagy.
Main Methods:
- Assessing mitochondrial damage and reactive oxygen species (ROS) production post-PFV infection.
- Evaluating the role of PFV Gag protein in mitophagy.
- Investigating the involvement of the PINK1-Parkin pathway and Rab5a.
- Utilizing gene overexpression and knockdown techniques.
Main Results:
- PFV infection causes time-dependent mitochondrial damage and increases mitochondrial ROS (mtROS).
- PFV Gag protein is essential for triggering mitophagy, causing mitochondrial damage and mitophagy in a dose-dependent manner.
- Gag activates the PINK1-Parkin pathway, and Parkin knockdown inhibits Gag-induced mitophagy.
- Rab5a is upregulated by Gag, and its inhibition reverses Gag-induced mitophagy.
Conclusions:
- PFV infection induces mitophagy, a process mediated by the viral Gag protein.
- Gag induces Parkin-dependent mitophagy, involving the upregulation of Rab5a.
- Findings provide insights into PFV infection mechanisms and virus-host interactions.
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