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A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization
Author(s) -
Lee HR.,
Cho Y. Y.,
Lee G. Y.,
You Dg.,
Yoo Y. D.,
Kim Y. J.
Publication year - 2018
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12831
Subject(s) - membrane potential , microbiology and biotechnology , mitochondrial permeability transition pore , inner mitochondrial membrane , mitochondrion , transmembrane protein , intracellular , biology , hepatitis b virus , bacterial outer membrane , chemistry , biochemistry , virus , virology , apoptosis , receptor , escherichia coli , programmed cell death , gene
Summary Hepatitis B virus X protein ( HB x) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HB x induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane‐mimic liposomes to observe the direct effects of HB x on membranes. We found that HB x induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial‐targeting sequence was sufficient for this process. Membrane permeabilization was inhibited by nonselective channel blockers or by N ‐(n‐nonyl)deoxynojirimycin ( N N ‐ DNJ ), a viroporin inhibitor. Moreover, N N ‐ DNJ inhibited HB x‐induced mitochondrial depolarization in Huh‐7 cells. Based on the results of this study, we can postulate that the HB x protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HB x targeting during HBV treatment.