Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence

Seong-Jun Kima, Gulam H. Syeda, Mohsin Khana, Wei-Wei Chiua, Muhammad

A. Sohailb, Robert G. Gishc, and Aleem Siddiquia.

 Proc Natl Acad Sci U S A. 2014 Apr 29; 111(17): 6413-8.

Speaker: Chou-Chen Chang (張肇宸)                          Time: 14:00~15:00, Dec. 24, 2014

Commentator: Dr. Hsiao-Sheng Liu (劉校生 教授)   Place: Room 601

Abstract:

Mitochondrial dynamics is tightly regulated in response to biophysical and pathophysiological changes, such as cellular stresses, viral infections, and nutrient supply alterations. A balance of mitochondrial dynamics contributes to keeping healthy and functional mitochondria in the cell. Since that, mitochondrial dynamics has been shown to play critical roles in fatty acid synthesis, calcium homeostasis, and apoptosis induction [1]. Hepatitis C virus (HCV) infects over 170 million people worldwide. Chronic infection occurs in 50–80% of cases and eventually leads to cirrhosis, fibrosis and hepatocellular carcinoma. However, the lifecycle and pathogenesis of HCV infection are only partly understood. Liver tissues from patients with chronic hepatitis C frequently exhibit traits of mitochondrial injury such as swollen, ruptured, and empty mitochondria [2]. Hence, survival of HCV-infected cells might rely on the ability in clearance of dysfunctional mitochondria. To investigate whether HCV infection alters mitochondrial dynamics, metabolism, and physiology, Huh7 cells were infected with HCV and the mitochondrial morphology was monitored. The authors found that HCV-infected cells displayed distinct fragmented mitochondria (mitochondrial fission) resulting from the Ser616-phosphorylation of dynamin-related protein 1 (Drp1), a key regulatory factor of mitochondria fission processes. The phosphorylated Drp1 caused its subsequent translocation to the mitochondria, followed by mitophagy (autophagy of mitochondria) to eliminate malfunctioned mitochondria. This paper demonstrated that HCV induces Drp1-mediated mitochondrial fission and mitophagy to protect cell from apoptosis. This may contribute to the growing list of the mechanisms in HCV persistent infection.

References:

1.     Kim SJ, et al. (2013). Hepatitis C virus induces the mitochondrial translocation of Parkin and subsequent mitophagy. PLoS Pathog 9(3): e1003285.

2.     Pawlotsky JM. (2004). Pathophysiology of hepatitis C virus infection and related liver disease. Trends Microbiol 12(2): 96–102.