ABSTRACT

Mitochondrion is a multifunctional organelle, which plays a central role in vital cellular signaling events including cellular homeostasis. Many viruses target mitochondria to facilitate viral proliferation and mitochondrial aberrations incurred during viral infections, which form the basis for the onset of disease pathogenesis. Alterations to the ultrastructure and function of mitochondria are due to a typical phenotype commonly observed in chronic viral hepatitis caused by hepatitis B and C viruses (HBV and HCV). Both HBV and HCV induce endoplasmic reticulum and oxidative stress that perturb cellular calcium homeostasis and trigger mitochondrial damage and injury. Recent studies demonstrate that HBV and HCV disrupt host cell mitochondrial dynamics and upregulate mitochondrial quality control pathways to eliminate mitochondria damaged during the course of infection. Both HBV and HCV induce mitochondrial ssion by triggering the mitochondrial recruitment of ssion protein dynamin-related protein 1 (Drp1), which allows the segregation of

Abstract .................................................................................................................. 327 Introduction ............................................................................................................ 328 Hepatitis B Virus .................................................................................................... 329 Hepatitis C Virus .................................................................................................... 330 Physiological Perturbation Associated with HBV and HCV Infections ................ 331 Mitochondrial Dynamics: Fission, Fusion, and Mitophagy................................... 333 HBV and HCV Infections and Mitochondrial Dynamics ...................................... 336 HBV and HCV Infections and Mitophagy ............................................................. 337 Mitochondrial Dynamics and Mitophagy: HBV/HCV Viral Persistence .............. 338 Mitochondrial Dynamics: Innate Immune Signaling and Inammasome ............. 338 Mitochondrial Dysfunctions: Viral Hepatitis and Nonalcoholic Steatohepatitits (NASH) ........................................................................................340 Conclusion .............................................................................................................340 Acknowledgments .................................................................................................. 341 References .............................................................................................................. 341

damaged mitochondria that are subsequently eliminated by Parkin-dependent, mitochondria-selective autophagy or mitophagy. HBV-and HCV-triggered alterations of mitochondrial dynamics functionally contribute to viral persistence by attenuating mitochondria-mediated apoptosis and innate immune signaling. In this chapter, we discuss the latest observations made in the eld of mitochondrial dynamics during HBV and HCV infection and demonstrate the emerging role of mitochondrial dynamics in chronic viral hepatitis and liver disease pathogenesis.