A new view of the lethal apoptotic pore.
Cell death by apoptosis is indispensable for proper development and tissue homeostasis in all multicellular organisms, and its deregulation plays a key role in cancer and many other diseases. A crucial event in apoptosis is the formation of protein-permeable pores in the outer mitochondrial membrane...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049484/pdf/?tool=EBI |
| _version_ | 1828955752011661312 |
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| author | Gorka Basañez Lucian Soane J Marie Hardwick |
| author_facet | Gorka Basañez Lucian Soane J Marie Hardwick |
| author_sort | Gorka Basañez |
| collection | DOAJ |
| description | Cell death by apoptosis is indispensable for proper development and tissue homeostasis in all multicellular organisms, and its deregulation plays a key role in cancer and many other diseases. A crucial event in apoptosis is the formation of protein-permeable pores in the outer mitochondrial membrane that release cytochrome c and other apoptosis-promoting factors into the cytosol. Research efforts over the past two decades have established that apoptotic pores require BCL-2 family proteins, with the proapoptotic BAX-type proteins being direct effectors of pore formation. Accumulating evidence indicates that other cellular components also cooperate with BCL-2 family members to regulate the apoptotic pore. Despite this knowledge, the molecular pathway leading to apoptotic pore formation at the outer mitochondrial membrane and the precise nature of this outer membrane pore remain enigmatic. In this issue of PLOS Biology, Kushnareva and colleagues describe a novel kinetic analysis of the dynamics of BAX-dependent apoptotic pore formation recapitulated in native mitochondrial outer membranes. Their study reveals the existence of a hitherto unknown outer mitochondrial membrane factor that is critical for BAX-mediated apoptotic pore formation, and challenges the currently popular view that the apoptotic pore is a purely proteinaceous multimeric assembly of BAX proteins. It also supports the notion that membrane remodeling events are implicated in the formation of a lipid-containing apoptotic pore. |
| first_indexed | 2024-12-14T07:57:50Z |
| format | Article |
| id | doaj.art-d06e94dfc07a43579177eb136fbb76e8 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-14T07:57:50Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-d06e94dfc07a43579177eb136fbb76e82022-12-21T23:10:31ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852012-01-01109e100139910.1371/journal.pbio.1001399A new view of the lethal apoptotic pore.Gorka BasañezLucian SoaneJ Marie HardwickCell death by apoptosis is indispensable for proper development and tissue homeostasis in all multicellular organisms, and its deregulation plays a key role in cancer and many other diseases. A crucial event in apoptosis is the formation of protein-permeable pores in the outer mitochondrial membrane that release cytochrome c and other apoptosis-promoting factors into the cytosol. Research efforts over the past two decades have established that apoptotic pores require BCL-2 family proteins, with the proapoptotic BAX-type proteins being direct effectors of pore formation. Accumulating evidence indicates that other cellular components also cooperate with BCL-2 family members to regulate the apoptotic pore. Despite this knowledge, the molecular pathway leading to apoptotic pore formation at the outer mitochondrial membrane and the precise nature of this outer membrane pore remain enigmatic. In this issue of PLOS Biology, Kushnareva and colleagues describe a novel kinetic analysis of the dynamics of BAX-dependent apoptotic pore formation recapitulated in native mitochondrial outer membranes. Their study reveals the existence of a hitherto unknown outer mitochondrial membrane factor that is critical for BAX-mediated apoptotic pore formation, and challenges the currently popular view that the apoptotic pore is a purely proteinaceous multimeric assembly of BAX proteins. It also supports the notion that membrane remodeling events are implicated in the formation of a lipid-containing apoptotic pore.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049484/pdf/?tool=EBI |
| spellingShingle | Gorka Basañez Lucian Soane J Marie Hardwick A new view of the lethal apoptotic pore. PLoS Biology |
| title | A new view of the lethal apoptotic pore. |
| title_full | A new view of the lethal apoptotic pore. |
| title_fullStr | A new view of the lethal apoptotic pore. |
| title_full_unstemmed | A new view of the lethal apoptotic pore. |
| title_short | A new view of the lethal apoptotic pore. |
| title_sort | new view of the lethal apoptotic pore |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049484/pdf/?tool=EBI |
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