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Article

BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition

by
Shujie Song
1,2,3,
Zhiying Jiang
2,
David Ethan Spezia-Lindner
4,
Ting Liang
2,4,
Chang Xu
5,
Haifeng Wang
3,
Ye Tian
3,* and
Yidong Bai
2,4,*
1
School of Public Health, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
2
Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
3
No. 3 Hospital, the Affiliated Hospital of Northwest University School of Medicine, Xi’an 710018, Shaanxi, China
4
Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX 78258, USA
5
First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(5), 1158; https://doi.org/10.3390/cells9051158
Submission received: 22 March 2020 / Revised: 28 April 2020 / Accepted: 28 April 2020 / Published: 7 May 2020
(This article belongs to the Section Mitochondria)
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Abstract

Epstein–Barr virus (EBV) is a major contributor to nasopharyngeal carcinoma (NPC) tumorigenesis. Mitochondria have been shown to be a target for tumor viral invasion, and to mediate viral tumorigenesis. In this study, we detected that mitochondrial morphological changes in tumor tissues of NPC patients infected with EBV were accompanied by an elevated expression of BHRF1, an EBV encoded protein homologue to Bcl-2. High expression of BHRF1 in human NPC cell lines enhanced tumorigenesis and metastasis features. With BHRF1 localized to mitochondria, its expression induced cyclophlin D dependent mitochondrial membrane permeabilization transition (MMPT). The MMPT further modulated mitochondrial function, increased ROS production and activated mitophagy, leading to enhanced tumorigenesis. Altogether, our results indicated that EBV-encoded BHRF1 plays an important role in NPC tumorigenesis through regulating cyclophlin D dependent MMPT.
Keywords: NPC; EBV; BHRF1; mitochondria; mitochondrial membrane permeabilization transition (MMPT); mitophagy NPC; EBV; BHRF1; mitochondria; mitochondrial membrane permeabilization transition (MMPT); mitophagy
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MDPI and ACS Style

Song, S.; Jiang, Z.; Spezia-Lindner, D.E.; Liang, T.; Xu, C.; Wang, H.; Tian, Y.; Bai, Y. BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition. Cells 2020, 9, 1158. https://doi.org/10.3390/cells9051158

AMA Style

Song S, Jiang Z, Spezia-Lindner DE, Liang T, Xu C, Wang H, Tian Y, Bai Y. BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition. Cells. 2020; 9(5):1158. https://doi.org/10.3390/cells9051158

Chicago/Turabian Style

Song, Shujie, Zhiying Jiang, David Ethan Spezia-Lindner, Ting Liang, Chang Xu, Haifeng Wang, Ye Tian, and Yidong Bai. 2020. "BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition" Cells 9, no. 5: 1158. https://doi.org/10.3390/cells9051158

APA Style

Song, S., Jiang, Z., Spezia-Lindner, D. E., Liang, T., Xu, C., Wang, H., Tian, Y., & Bai, Y. (2020). BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition. Cells, 9(5), 1158. https://doi.org/10.3390/cells9051158

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