Hepatitis C virus p7 induces mitochondrial depolarization of isolated liver mitochondria

Deok Gyun You, Hye Ra Lee, Won Ki Kim, Hyung Jung Kim, Gi Young Lee, Young Do Yoo

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    Hepatitis C virus (HCV)-encoded protein p7 is a viroporin that acts as an ion channel and is indispensable for HCV particle production. Although the main target of HCV p7 is the endoplasmic reticulum, it also targets mitochondria. HCV-infected cells show mitochondrial depolarization and ATP depletion; however, the function of HCV p7 in mitochondria is not fully understood. The present study demonstrated that treatment of isolated mouse liver mitochondria with the synthesized HCV p7 protein induced mitochondrial dysfunction. It also demonstrated that HCV p7 targeted isolated mouse liver mitochondria and induced mitochondrial depolarization. In addition, HCV p7 triggered matrix acidification and, ultimately, a decrease in ATP synthesis in isolated mitochondria. These findings indicate that targeting of mitochondria by HCV p7 in infected cells causes mitochondrial dysfunction to support HCV particle production. The present study provided evidence for the role of HCV p7 in mitochondria, and may lead to the development of novel strategies for HCV therapy.

    Original languageEnglish
    Pages (from-to)9533-9538
    Number of pages6
    JournalMolecular Medicine Reports
    Volume16
    Issue number6
    DOIs
    Publication statusPublished - 2017 Dec

    Bibliographical note

    Funding Information:
    The present study was supported by the National Research Foundation of Korea grant funded by the Korean government (grant no. NRF-2013R1A1A2063171), by Basic Science Research Program through the National Research Foundation funded by the Ministry of Education, Science and Technology (grant no. NRF-2013R1A1A2009792), by Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education (grant no. NRF-2017R1D1A1B03032322), and by a grant from the Korea Health Technology R&D Project (grant no. HI15C2796) of the Korea Health Industry Development Institute, which is funded by the Ministry of Health and Welfare, Republic of Korea.

    Keywords

    • Hepatitis
    • Hepatitis C virus p7
    • Mitochondria
    • Mitochondrial depolarization
    • Mitochondrial dysfunction

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Genetics
    • Oncology
    • Cancer Research

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