Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1
ABSTRACTViral control of mitochondria via mitophagy has a dampening effect on mitochondrion-mediated innate immune responses. We previously found that human herpesvirus 8 (HHV-8) could activate mitophagy via its lytic gene product vIRF-1 (viral interferon regulatory factor 1). Mechanistically, we pr...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2023.2281135 |
| _version_ | 1797627766307291136 |
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| author | Mai Tram Vo Young Bong Choi |
| author_facet | Mai Tram Vo Young Bong Choi |
| author_sort | Mai Tram Vo |
| collection | DOAJ |
| description | ABSTRACTViral control of mitochondria via mitophagy has a dampening effect on mitochondrion-mediated innate immune responses. We previously found that human herpesvirus 8 (HHV-8) could activate mitophagy via its lytic gene product vIRF-1 (viral interferon regulatory factor 1). Mechanistically, we previously demonstrated that vIRF-1 interacts with the mitophagic proteins BNIP3L (BCL2 interacting protein 3 like) and TUFM (Tu translation elongation factor, mitochondrial). Despite these significant findings, however, the precise molecular mechanisms underlying vIRF-1-activated mitophagy, particularly with core components of the autophagy machinery, remained to be fully elucidated. We recently reported that vIRF-1 binds preferentially and directly to GABARAPL1 (GABA type A receptor associated protein like 1) in a noncanonical manner, and this interaction is essential for virus-productive replication. Furthermore, we found that BNIP3L is a crucial factor that promotes vIRF-1 oligomerization and associated mitophagy activation, including GABARAPL1 interaction with vIRF-1 and TUFM dimerization. Together, our findings deepen our understanding of lytic infection-induced mitophagy and provide the key protein-protein interactions involved in vIRF-1-mediated mitophagy.Abbreviations: ATG8, autophagy-related gene 8; BNIP3L, BCL2 interacting protein 3 like; HHV-8, human herpesvirus 8; GABARAP, GABA type A receptor associated protein; GABARAPL1, GABARAP-like 1; LC3, microtubule-associated protein 1 light chain 3; LIR, LC3-interacting region; Nix, NIP3-like protein X; TUFM, Tu translation elongation factor, mitochondria; vIRF-1, viral interferon regulatory factor 1; UIM, ubiquitin-interacting motif; VIR, vIRF-1-interacting region. |
| first_indexed | 2024-03-11T10:29:07Z |
| format | Article |
| id | doaj.art-d60ef35504384625b030468ea9507687 |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-03-11T10:29:07Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-d60ef35504384625b030468ea95076872023-11-15T05:09:50ZengTaylor & Francis GroupAutophagy Reports2769-41272023-12-012110.1080/27694127.2023.2281135Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1Mai Tram Vo0Young Bong Choi1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAABSTRACTViral control of mitochondria via mitophagy has a dampening effect on mitochondrion-mediated innate immune responses. We previously found that human herpesvirus 8 (HHV-8) could activate mitophagy via its lytic gene product vIRF-1 (viral interferon regulatory factor 1). Mechanistically, we previously demonstrated that vIRF-1 interacts with the mitophagic proteins BNIP3L (BCL2 interacting protein 3 like) and TUFM (Tu translation elongation factor, mitochondrial). Despite these significant findings, however, the precise molecular mechanisms underlying vIRF-1-activated mitophagy, particularly with core components of the autophagy machinery, remained to be fully elucidated. We recently reported that vIRF-1 binds preferentially and directly to GABARAPL1 (GABA type A receptor associated protein like 1) in a noncanonical manner, and this interaction is essential for virus-productive replication. Furthermore, we found that BNIP3L is a crucial factor that promotes vIRF-1 oligomerization and associated mitophagy activation, including GABARAPL1 interaction with vIRF-1 and TUFM dimerization. Together, our findings deepen our understanding of lytic infection-induced mitophagy and provide the key protein-protein interactions involved in vIRF-1-mediated mitophagy.Abbreviations: ATG8, autophagy-related gene 8; BNIP3L, BCL2 interacting protein 3 like; HHV-8, human herpesvirus 8; GABARAP, GABA type A receptor associated protein; GABARAPL1, GABARAP-like 1; LC3, microtubule-associated protein 1 light chain 3; LIR, LC3-interacting region; Nix, NIP3-like protein X; TUFM, Tu translation elongation factor, mitochondria; vIRF-1, viral interferon regulatory factor 1; UIM, ubiquitin-interacting motif; VIR, vIRF-1-interacting region.https://www.tandfonline.com/doi/10.1080/27694127.2023.2281135BNIP3LHuman herpesvirus 8GABARAPL1MitochondriaMitophagyNix |
| spellingShingle | Mai Tram Vo Young Bong Choi Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1 Autophagy Reports BNIP3L Human herpesvirus 8 GABARAPL1 Mitochondria Mitophagy Nix |
| title | Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1 |
| title_full | Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1 |
| title_fullStr | Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1 |
| title_full_unstemmed | Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1 |
| title_short | Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1 |
| title_sort | herpesvirus lytic infection induced mitophagy via viral interferon regulatory factor 1 |
| topic | BNIP3L Human herpesvirus 8 GABARAPL1 Mitochondria Mitophagy Nix |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2023.2281135 |
| work_keys_str_mv | AT maitramvo herpesviruslyticinfectioninducedmitophagyviaviralinterferonregulatoryfactor1 AT youngbongchoi herpesviruslyticinfectioninducedmitophagyviaviralinterferonregulatoryfactor1 |