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Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy
- Source :
- Cells, Volume 8, Issue 4, Cells, Vol 8, Iss 4, p 290 (2019)
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Mitophagy is a selective form of autophagy, targeting damaged mitochondria for lysosomal degradation. Although HCV infection has been shown to induce mitophagy, the precise underlying mechanism and the effector protein responsible remain unclear. Herein, we demonstrated that the HCV non-structural protein 5A (NS5A) plays a key role in regulating cellular mitophagy. Specifically, the expression of HCV NS5A in the hepatoma cells triggered hallmarks of mitophagy including mitochondrial fragmentation, loss of mitochondrial membrane potential, and Parkin translocation to the mitochondria. Furthermore, mitophagy induction through the expression of NS5A led to an increase in autophagic flux as demonstrated by an accumulation of LC3II in the presence of bafilomycin and a time-dependent decrease in p62 protein level. Intriguingly, the expression of NS5A concomitantly enhanced reactive oxygen species (ROS) production, and treatment with an antioxidant attenuated the NS5A-induced mitophagy event. These phenomena are similarly recapitulated in the NS5A-expressing HCV subgenomic replicon cells. Finally, we demonstrated that expression of HCV core, which has been documented to inhibit mitophagy, blocked the mitophagy induction both in cells harboring HCV replicating subgenomes or expressing NS5A alone. Our results, therefore, identified a new role for NS5A as an important regulator of HCV-induced mitophagy and have implications to broadening our understanding of the HCV-mitophagy interplay.
- Subjects :
- 0301 basic medicine
Ubiquitin-Protein Ligases
viruses
Hepacivirus
Viral Nonstructural Proteins
Mitochondrion
NS5A
Article
Parkin
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Mitophagy
Autophagy
Humans
lcsh:QH301-705.5
Membrane Potential, Mitochondrial
chemistry.chemical_classification
Reactive oxygen species
Effector
Chemistry
virus diseases
Bafilomycin
General Medicine
biochemical phenomena, metabolism, and nutrition
Lipids
mitochondrial dynamics
digestive system diseases
Mitochondria
Cell biology
Protein Transport
mitophagy
030104 developmental biology
lcsh:Biology (General)
030220 oncology & carcinogenesis
HCV
Replicon
Reactive Oxygen Species
Microtubule-Associated Proteins
Subjects
Details
- ISSN :
- 20734409
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....48a888b6cb16efa8f344cbfebda9a316