Hepatitis B virus X protein induces size-selective membrane permeabilization through interaction with cardiolipin

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)729-737
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Issue number4
DOIs
Publication statusPublished - 2019 Apr 1

Keywords

  • Cardiolipin
  • HBx
  • Hepatitis B virus
  • Membrane permeabilization

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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