Hepatitis B virus X protein induces size-selective membrane permeabilization through interaction with cardiolipin |
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Authors: | Deok-gyun You Young Youn Cho Hye-Ra Lee Jeong-Hoon Lee Su Jong Yu Jung-Hwan Yoon Young Do Yoo Yoon Jun Kim Gi Young Lee |
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Institution: | 1. Laboratory of Molecular Cell Biology, Graduate School of Medicine, College of Medicine, Korea University, Seoul 02841, Republic of Korea;2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea;3. Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea |
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Abstract: | Hepatitis B virus X protein (HBx) functions in a variety of cellular events during the HBV life cycle. In a previous study, we reported that the HBx protein is sufficient to induce mitochondrial membrane permeabilization; however, the exact mechanism of HBx-induced mitochondrial membrane permeabilization has been not proposed. In this study, we report that HBx specifically targets cardiolipin (CL) and induces membrane permeabilization depending on CL concentration in mitochondrial outer membrane–mimic artificial liposomes. Interestingly, HBx-induced membrane permeabilization was enhanced by liposomes containing phosphatidylethanolamine, which plays a crucial role in forming a negative curvature on the membrane. We also show that the 68-117 region of HBx, which interacts with mitochondria, is necessary for membrane permeabilization. We examined the size of the pores formed by HBx and found that HBx permeates fluorescent dyes depending on the hydrodynamic diameter with a pore size of approximately 10 nm. The results of this study suggest that CL is necessary for HBx-induced membrane permeabilization and provide important information that suggests a new strategy for anti-HBV therapy. |
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Keywords: | Corresponding authors Hepatitis B virus HBx Membrane permeabilization Cardiolipin |
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