A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization

H. R. Lee, Y. Y. Cho, G. Y. Lee, D. g. You, Young Do Yoo, Y. J. Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Hepatitis B virus X protein (HBx) 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 HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx 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 (NN-DNJ), a viroporin inhibitor. Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.

Original languageEnglish
JournalJournal of Viral Hepatitis
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Mitochondrial Membranes
Membranes
Intracellular Signaling Peptides and Proteins
Liposomes
Proteins
hepatitis B virus X protein
Infection
N-nonyl-1-deoxynojirimycin
Therapeutics

Keywords

  • Hepatitis B virus X protein
  • Membrane permeabilization
  • Viroporin

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization. / Lee, H. R.; Cho, Y. Y.; Lee, G. Y.; You, D. g.; Yoo, Young Do; Kim, Y. J.

In: Journal of Viral Hepatitis, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Cho, Y. Y.

AU - Lee, G. Y.

AU - You, D. g.

AU - Yoo, Young Do

AU - Kim, Y. J.

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N2 - Hepatitis B virus X protein (HBx) 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 HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx 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 (NN-DNJ), a viroporin inhibitor. Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.

AB - Hepatitis B virus X protein (HBx) 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 HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx 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 (NN-DNJ), a viroporin inhibitor. Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.

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