Bakuchiol targets mitochondrial proteins, prohibitins and voltage-dependent anion channels: New insights into developing antiviral agents Article Swipe
Masaki Shoji
,
Tomoyuki Esumi
,
Takeshi Masuda
,
Narue Tanaka
,
Risa Okamoto
,
Hinako Sato
,
Mihiro Watanabe
,
Etsuhisa Takahashi
,
Hiroshi Kido
,
Sumio Ohtsuki
,
Takashi Kuzuhara
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.jbc.2024.105632
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.jbc.2024.105632
We previously reported that bakuchiol, a phenolic isoprenoid anticancer compound, and its analogs exert anti-influenza activity. However, the proteins targeted by bakuchiol remain unclear. Here, we investigated the chemical structures responsible for the anti-influenza activity of bakuchiol and found that all functional groups and C6 chirality of bakuchiol were required for its anti-influenza activity. Based on these results, we synthesized a molecular probe containing a biotin tag bound to the C1 position of bakuchiol. With this probe, we performed a pulldown assay for Madin-Darby canine kidney cell lysates and purified the specific bakuchiol-binding proteins with SDS-PAGE. Using nanoLC-MS/MS analysis, we identified prohibitin (PHB) 2, voltage-dependent anion channel (VDAC) 1, and VDAC2 as binding proteins of bakuchiol. We confirmed the binding of bakuchiol to PHB1, PHB2, and VDAC2 in vitro using Western blot analysis. Immunofluorescence analysis showed that bakuchiol was bound to PHBs and VDAC2 in cells and colocalized in the mitochondria. The knockdown of PHBs or VDAC2 by transfection with specific siRNAs, along with bakuchiol cotreatment, led to significantly reduced influenza nucleoprotein expression levels and viral titers in the conditioned medium of virus-infected Madin-Darby canine kidney cells, compared to the levels observed with transfection or treatment alone. These findings indicate that reducing PHBs or VDAC2 protein, combined with bakuchiol treatment, additively suppressed the growth of influenza virus. Our findings indicate that bakuchiol exerts anti-influenza activity via a novel mechanism involving these mitochondrial proteins, providing new insight for developing anti-influenza agents.
Related Topics
Concepts
Voltage-dependent anion channel
Cell biology
Chemistry
Mitochondrion
Virology
Biology
Computational biology
Biochemistry
Escherichia coli
Bacterial outer membrane
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.jbc.2024.105632
- http://www.jbc.org/article/S0021925824000085/pdf
- OA Status
- gold
- Cited By
- 4
- References
- 75
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390674646
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4390674646Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.jbc.2024.105632Digital Object Identifier
- Title
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Bakuchiol targets mitochondrial proteins, prohibitins and voltage-dependent anion channels: New insights into developing antiviral agentsWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
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2024-01-08Full publication date if available
- Authors
-
Masaki Shoji, Tomoyuki Esumi, Takeshi Masuda, Narue Tanaka, Risa Okamoto, Hinako Sato, Mihiro Watanabe, Etsuhisa Takahashi, Hiroshi Kido, Sumio Ohtsuki, Takashi KuzuharaList of authors in order
- Landing page
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https://doi.org/10.1016/j.jbc.2024.105632Publisher landing page
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https://www.jbc.org/article/S0021925824000085/pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.jbc.org/article/S0021925824000085/pdfDirect OA link when available
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Voltage-dependent anion channel, Cell biology, Chemistry, Mitochondrion, Virology, Biology, Computational biology, Biochemistry, Escherichia coli, Bacterial outer membrane, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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4Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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75Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.this | 75 |
| abstract_inverted_index.were | 48 |
| abstract_inverted_index.with | 94, 159, 163, 192, 207 |
| abstract_inverted_index.(PHB) | 102 |
| abstract_inverted_index.Based | 54 |
| abstract_inverted_index.Here, | 24 |
| abstract_inverted_index.PHB1, | 123 |
| abstract_inverted_index.PHB2, | 124 |
| abstract_inverted_index.These | 197 |
| abstract_inverted_index.Using | 96 |
| abstract_inverted_index.VDAC2 | 110, 126, 143, 156, 204 |
| abstract_inverted_index.along | 162 |
| abstract_inverted_index.anion | 105 |
| abstract_inverted_index.assay | 81 |
| abstract_inverted_index.bound | 67, 139 |
| abstract_inverted_index.cells | 145 |
| abstract_inverted_index.exert | 13 |
| abstract_inverted_index.found | 38 |
| abstract_inverted_index.novel | 227 |
| abstract_inverted_index.probe | 62 |
| abstract_inverted_index.these | 56, 230 |
| abstract_inverted_index.using | 129 |
| abstract_inverted_index.viral | 175 |
| abstract_inverted_index.vitro | 128 |
| abstract_inverted_index.(VDAC) | 107 |
| abstract_inverted_index.alone. | 196 |
| abstract_inverted_index.biotin | 65 |
| abstract_inverted_index.canine | 84, 184 |
| abstract_inverted_index.cells, | 186 |
| abstract_inverted_index.exerts | 222 |
| abstract_inverted_index.groups | 42 |
| abstract_inverted_index.growth | 213 |
| abstract_inverted_index.kidney | 85, 185 |
| abstract_inverted_index.levels | 173, 190 |
| abstract_inverted_index.medium | 180 |
| abstract_inverted_index.probe, | 76 |
| abstract_inverted_index.remain | 22 |
| abstract_inverted_index.showed | 135 |
| abstract_inverted_index.titers | 176 |
| abstract_inverted_index.virus. | 216 |
| abstract_inverted_index.Western | 130 |
| abstract_inverted_index.agents. | 239 |
| abstract_inverted_index.analogs | 12 |
| abstract_inverted_index.binding | 112, 119 |
| abstract_inverted_index.channel | 106 |
| abstract_inverted_index.insight | 235 |
| abstract_inverted_index.lysates | 87 |
| abstract_inverted_index.reduced | 169 |
| abstract_inverted_index.siRNAs, | 161 |
| abstract_inverted_index.However, | 16 |
| abstract_inverted_index.activity | 34, 224 |
| abstract_inverted_index.analysis | 134 |
| abstract_inverted_index.chemical | 28 |
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| abstract_inverted_index.compared | 187 |
| abstract_inverted_index.findings | 198, 218 |
| abstract_inverted_index.indicate | 199, 219 |
| abstract_inverted_index.observed | 191 |
| abstract_inverted_index.phenolic | 6 |
| abstract_inverted_index.position | 71 |
| abstract_inverted_index.protein, | 205 |
| abstract_inverted_index.proteins | 18, 93, 113 |
| abstract_inverted_index.pulldown | 80 |
| abstract_inverted_index.purified | 89 |
| abstract_inverted_index.reducing | 201 |
| abstract_inverted_index.reported | 2 |
| abstract_inverted_index.required | 49 |
| abstract_inverted_index.results, | 57 |
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| abstract_inverted_index.targeted | 19 |
| abstract_inverted_index.unclear. | 23 |
| abstract_inverted_index.SDS-PAGE. | 95 |
| abstract_inverted_index.activity. | 15, 53 |
| abstract_inverted_index.analysis, | 98 |
| abstract_inverted_index.analysis. | 132 |
| abstract_inverted_index.bakuchiol | 21, 36, 47, 121, 137, 164, 208, 221 |
| abstract_inverted_index.chirality | 45 |
| abstract_inverted_index.compound, | 9 |
| abstract_inverted_index.confirmed | 117 |
| abstract_inverted_index.influenza | 170, 215 |
| abstract_inverted_index.involving | 229 |
| abstract_inverted_index.knockdown | 152 |
| abstract_inverted_index.mechanism | 228 |
| abstract_inverted_index.molecular | 61 |
| abstract_inverted_index.performed | 78 |
| abstract_inverted_index.proteins, | 232 |
| abstract_inverted_index.providing | 233 |
| abstract_inverted_index.treatment | 195 |
| abstract_inverted_index.additively | 210 |
| abstract_inverted_index.anticancer | 8 |
| abstract_inverted_index.bakuchiol, | 4 |
| abstract_inverted_index.bakuchiol. | 73, 115 |
| abstract_inverted_index.containing | 63 |
| abstract_inverted_index.developing | 237 |
| abstract_inverted_index.expression | 172 |
| abstract_inverted_index.functional | 41 |
| abstract_inverted_index.identified | 100 |
| abstract_inverted_index.isoprenoid | 7 |
| abstract_inverted_index.previously | 1 |
| abstract_inverted_index.prohibitin | 101 |
| abstract_inverted_index.structures | 29 |
| abstract_inverted_index.suppressed | 211 |
| abstract_inverted_index.treatment, | 209 |
| abstract_inverted_index.Madin-Darby | 83, 183 |
| abstract_inverted_index.colocalized | 147 |
| abstract_inverted_index.conditioned | 179 |
| abstract_inverted_index.responsible | 30 |
| abstract_inverted_index.synthesized | 59 |
| abstract_inverted_index.cotreatment, | 165 |
| abstract_inverted_index.investigated | 26 |
| abstract_inverted_index.nanoLC-MS/MS | 97 |
| abstract_inverted_index.transfection | 158, 193 |
| abstract_inverted_index.mitochondria. | 150 |
| abstract_inverted_index.mitochondrial | 231 |
| abstract_inverted_index.nucleoprotein | 171 |
| abstract_inverted_index.significantly | 168 |
| abstract_inverted_index.anti-influenza | 14, 33, 52, 223, 238 |
| abstract_inverted_index.virus-infected | 182 |
| abstract_inverted_index.bakuchiol-binding | 92 |
| abstract_inverted_index.voltage-dependent | 104 |
| abstract_inverted_index.Immunofluorescence | 133 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5021135285, https://openalex.org/A5045716624 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 11 |
| corresponding_institution_ids | https://openalex.org/I89098413 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.5799999833106995 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.77317777 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |