Next Article in Journal
Cellular and Animal Models of Striated Muscle Laminopathies
Next Article in Special Issue
Hepatitis C Virus Genetic Variability, Human Immune Response, and Genome Polymorphisms: Which Is the Interplay?
Previous Article in Journal
Mitochondrial Genetic Disorders: Cell Signaling and Pharmacological Therapies
Previous Article in Special Issue
Strategies to Circumvent Host Innate Immune Response by Hepatitis C Virus
Article

Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy

1
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
2
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3
Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada
4
Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
5
Integrated Laboratory, Center of Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
6
Core Facility, Taipei Medical University, Taipei 11031, Taiwan
7
Department of Pediatrics and Canadian Center for Vaccinology, Izaak Walton Killam Health Centre, Halifax, NS B3H 4R2, Canada
8
Department of Life Sciences, Tzu-Chi University, Hualien 970, Taiwan
9
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
*
Author to whom correspondence should be addressed.
Cells 2019, 8(4), 290; https://doi.org/10.3390/cells8040290
Received: 1 December 2018 / Revised: 12 March 2019 / Accepted: 26 March 2019 / Published: 29 March 2019
(This article belongs to the Special Issue Hepatitis C Virus and Host Interactions)
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. View Full-Text
Keywords: HCV; NS5A; mitophagy; Parkin; mitochondrial dynamics HCV; NS5A; mitophagy; Parkin; mitochondrial dynamics
Show Figures

Figure 1

MDPI and ACS Style

Jassey, A.; Liu, C.-H.; Changou, C.A.; Richardson, C.D.; Hsu, H.-Y.; Lin, L.-T. Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy. Cells 2019, 8, 290. https://doi.org/10.3390/cells8040290

AMA Style

Jassey A, Liu C-H, Changou CA, Richardson CD, Hsu H-Y, Lin L-T. Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy. Cells. 2019; 8(4):290. https://doi.org/10.3390/cells8040290

Chicago/Turabian Style

Jassey, Alagie, Ching-Hsuan Liu, Chun A. Changou, Christopher D. Richardson, Hsue-Yin Hsu, and Liang-Tzung Lin. 2019. "Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy" Cells 8, no. 4: 290. https://doi.org/10.3390/cells8040290

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop