The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved]
Bax and Bak, two functionally similar, pro-apoptotic proteins of the Bcl-2 family, are known as the gateway to apoptosis because of their requisite roles as effectors of mitochondrial outer membrane permeabilization (MOMP), a major step during mitochondria-dependent apoptosis. The mechanism of how c...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2020-08-01
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| Series: | F1000Research |
| Online Access: | https://f1000research.com/articles/9-935/v1 |
| _version_ | 1818959758070120448 |
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| author | Xu Luo Katelyn L. O'Neill Kai Huang |
| author_facet | Xu Luo Katelyn L. O'Neill Kai Huang |
| author_sort | Xu Luo |
| collection | DOAJ |
| description | Bax and Bak, two functionally similar, pro-apoptotic proteins of the Bcl-2 family, are known as the gateway to apoptosis because of their requisite roles as effectors of mitochondrial outer membrane permeabilization (MOMP), a major step during mitochondria-dependent apoptosis. The mechanism of how cells turn Bax/Bak from inert molecules into fully active and lethal effectors had long been the focal point of a major debate centered around two competing, but not mutually exclusive, models: direct activation and indirect activation. After intensive research efforts for over two decades, it is now widely accepted that to initiate apoptosis, some of the BH3-only proteins, a subclass of the Bcl-2 family, directly engage Bax/Bak to trigger their conformational transformation and activation. However, a series of recent discoveries, using previously unavailable CRISPR-engineered cell systems, challenge the basic premise that undergirds the consensus and provide evidence for a novel and surprisingly simple model of Bax/Bak activation: the membrane (lipids)-mediated spontaneous model. This review will discuss the evidence, rationale, significance, and implications of this new model. |
| first_indexed | 2024-12-20T11:46:43Z |
| format | Article |
| id | doaj.art-b05ac836e39044fbbd370f0520a44844 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-20T11:46:43Z |
| publishDate | 2020-08-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-b05ac836e39044fbbd370f0520a448442022-12-21T19:41:51ZengF1000 Research LtdF1000Research2046-14022020-08-01910.12688/f1000research.25607.128260The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved]Xu Luo0Katelyn L. O'Neill1Kai Huang2Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Alaska Medical Center, Omaha, ME, 68198-7696, USAEppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Alaska Medical Center, Omaha, ME, 68198-7696, USAEppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Alaska Medical Center, Omaha, ME, 68198-7696, USABax and Bak, two functionally similar, pro-apoptotic proteins of the Bcl-2 family, are known as the gateway to apoptosis because of their requisite roles as effectors of mitochondrial outer membrane permeabilization (MOMP), a major step during mitochondria-dependent apoptosis. The mechanism of how cells turn Bax/Bak from inert molecules into fully active and lethal effectors had long been the focal point of a major debate centered around two competing, but not mutually exclusive, models: direct activation and indirect activation. After intensive research efforts for over two decades, it is now widely accepted that to initiate apoptosis, some of the BH3-only proteins, a subclass of the Bcl-2 family, directly engage Bax/Bak to trigger their conformational transformation and activation. However, a series of recent discoveries, using previously unavailable CRISPR-engineered cell systems, challenge the basic premise that undergirds the consensus and provide evidence for a novel and surprisingly simple model of Bax/Bak activation: the membrane (lipids)-mediated spontaneous model. This review will discuss the evidence, rationale, significance, and implications of this new model.https://f1000research.com/articles/9-935/v1 |
| spellingShingle | Xu Luo Katelyn L. O'Neill Kai Huang The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved] F1000Research |
| title | The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved] |
| title_full | The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved] |
| title_fullStr | The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved] |
| title_full_unstemmed | The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved] |
| title_short | The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? [version 1; peer review: 3 approved] |
| title_sort | third model of bax bak activation a bcl 2 family feud finally resolved version 1 peer review 3 approved |
| url | https://f1000research.com/articles/9-935/v1 |
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