A novel autophagy inhibitor, bTBT, disturbs autophagosome formation
Macroautophagy (hereafter, autophagy) is a form of intracellular degradation in which autophagosome formation is systematically coordinated by multiple processes involving numerous autophagy-related gene (ATG) proteins. Autophagy-modulating compounds are valuable for understanding the molecular mech...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/27694127.2023.2194620 |
| _version_ | 1827818559669010432 |
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| author | Momoka Chiba Mai Yanagawa Yurika Oyama Shingo Harada Tetsuhiro Nemoto Akira Matsuura Eisuke Itakura |
| author_facet | Momoka Chiba Mai Yanagawa Yurika Oyama Shingo Harada Tetsuhiro Nemoto Akira Matsuura Eisuke Itakura |
| author_sort | Momoka Chiba |
| collection | DOAJ |
| description | Macroautophagy (hereafter, autophagy) is a form of intracellular degradation in which autophagosome formation is systematically coordinated by multiple processes involving numerous autophagy-related gene (ATG) proteins. Autophagy-modulating compounds are valuable for understanding the molecular mechanism of autophagy and its clinical application. Although several autophagy inhibitors have been identified, their inhibitory steps during autophagosome formation by the inhibitors are limited. Herein, we identified a novel autophagy inhibitor, bis-tributyltin (bTBT), which inhibits a unique step in autophagosome formation. In mammalian cells, bTBT treatment suppresses LC3 flux and accumulates most of ATG proteins, including LC3 and early ATG proteins (ULK1, ATG16L1, and WIPI2), in punctate structures. On the other hand, LAMP1, a lysosomal marker, did not co-localize with accumulated LC3 after bTBT treatment, indicating bTBT inhibits a late step of autophagosome formation. Stx17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein that mediates autophagosome–lysosome fusion, is usually recruited to LC3-positive structures after the dissociation of early ATG proteins. However, bTBT accumulates Stx17 and WIPI2 positive large autophagic structures and maintains the autophagic structures for much longer. In conclusion, we identified a novel type of autophagy inhibitor, bTBT, which disturbs autophagosome formation. |
| first_indexed | 2024-03-12T00:55:33Z |
| format | Article |
| id | doaj.art-c8f10b04c9c349e2a307d04cec2c8332 |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-03-12T00:55:33Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-c8f10b04c9c349e2a307d04cec2c83322023-09-14T13:24:41ZengTaylor & Francis GroupAutophagy Reports2769-41272023-12-012110.1080/27694127.2023.21946202194620A novel autophagy inhibitor, bTBT, disturbs autophagosome formationMomoka Chiba0Mai Yanagawa1Yurika Oyama2Shingo Harada3Tetsuhiro Nemoto4Akira Matsuura5Eisuke Itakura6Graduate school of Science and Engineering, Chiba UniversityGraduate School of Pharmaceutical Sciences, Chiba UniversityGraduate school of Science and Engineering, Chiba UniversityGraduate School of Pharmaceutical Sciences, Chiba UniversityGraduate School of Pharmaceutical Sciences, Chiba UniversityGraduate School of Science, Chiba UniversityGraduate School of Science, Chiba UniversityMacroautophagy (hereafter, autophagy) is a form of intracellular degradation in which autophagosome formation is systematically coordinated by multiple processes involving numerous autophagy-related gene (ATG) proteins. Autophagy-modulating compounds are valuable for understanding the molecular mechanism of autophagy and its clinical application. Although several autophagy inhibitors have been identified, their inhibitory steps during autophagosome formation by the inhibitors are limited. Herein, we identified a novel autophagy inhibitor, bis-tributyltin (bTBT), which inhibits a unique step in autophagosome formation. In mammalian cells, bTBT treatment suppresses LC3 flux and accumulates most of ATG proteins, including LC3 and early ATG proteins (ULK1, ATG16L1, and WIPI2), in punctate structures. On the other hand, LAMP1, a lysosomal marker, did not co-localize with accumulated LC3 after bTBT treatment, indicating bTBT inhibits a late step of autophagosome formation. Stx17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein that mediates autophagosome–lysosome fusion, is usually recruited to LC3-positive structures after the dissociation of early ATG proteins. However, bTBT accumulates Stx17 and WIPI2 positive large autophagic structures and maintains the autophagic structures for much longer. In conclusion, we identified a novel type of autophagy inhibitor, bTBT, which disturbs autophagosome formation.http://dx.doi.org/10.1080/27694127.2023.2194620autophagyinhibitorwipi2autophagosome formationbis-tributyltin |
| spellingShingle | Momoka Chiba Mai Yanagawa Yurika Oyama Shingo Harada Tetsuhiro Nemoto Akira Matsuura Eisuke Itakura A novel autophagy inhibitor, bTBT, disturbs autophagosome formation Autophagy Reports autophagy inhibitor wipi2 autophagosome formation bis-tributyltin |
| title | A novel autophagy inhibitor, bTBT, disturbs autophagosome formation |
| title_full | A novel autophagy inhibitor, bTBT, disturbs autophagosome formation |
| title_fullStr | A novel autophagy inhibitor, bTBT, disturbs autophagosome formation |
| title_full_unstemmed | A novel autophagy inhibitor, bTBT, disturbs autophagosome formation |
| title_short | A novel autophagy inhibitor, bTBT, disturbs autophagosome formation |
| title_sort | novel autophagy inhibitor btbt disturbs autophagosome formation |
| topic | autophagy inhibitor wipi2 autophagosome formation bis-tributyltin |
| url | http://dx.doi.org/10.1080/27694127.2023.2194620 |
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