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 language | English |
|---|---|
| Pages (from-to) | 729-737 |
| Number of pages | 9 |
| Journal | Biochimica et Biophysica Acta - Biomembranes |
| Volume | 1861 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2019 Apr 1 |
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Keywords
- Cardiolipin
- HBx
- Hepatitis B virus
- Membrane permeabilization
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Cell Biology
Cite this
Hepatitis B virus X protein induces size-selective membrane permeabilization through interaction with cardiolipin. / You, Deok gyun; Cho, Young Youn; Lee, Hye Ra; Lee, Jeong Hoon; Yu, Su Jong; Yoon, Jung Hwan; Yoo, Young Do; Kim, Yoon Jun; Lee, Gi Young.
In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1861, No. 4, 01.04.2019, p. 729-737.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hepatitis B virus X protein induces size-selective membrane permeabilization through interaction with cardiolipin
AU - You, Deok gyun
AU - Cho, Young Youn
AU - Lee, Hye Ra
AU - Lee, Jeong Hoon
AU - Yu, Su Jong
AU - Yoon, Jung Hwan
AU - Yoo, Young Do
AU - Kim, Yoon Jun
AU - Lee, Gi Young
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - Cardiolipin
KW - HBx
KW - Hepatitis B virus
KW - Membrane permeabilization
UR - http://www.scopus.com/inward/record.url?scp=85060309909&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060309909&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2019.01.006
DO - 10.1016/j.bbamem.2019.01.006
M3 - Article
VL - 1861
SP - 729
EP - 737
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
SN - 0005-2736
IS - 4
ER -