Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid.
Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activatin...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23418437/?tool=EBI |
| _version_ | 1818572874156343296 |
|---|---|
| author | Olivier Jalmar Liberty François-Moutal Ana-Jesus García-Sáez Mark Perry Thierry Granjon François Gonzalvez Eyal Gottlieb Jesus Ayala-Sanmartin Beate Klösgen Petra Schwille Patrice X Petit |
| author_facet | Olivier Jalmar Liberty François-Moutal Ana-Jesus García-Sáez Mark Perry Thierry Granjon François Gonzalvez Eyal Gottlieb Jesus Ayala-Sanmartin Beate Klösgen Petra Schwille Patrice X Petit |
| author_sort | Olivier Jalmar |
| collection | DOAJ |
| description | Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria. |
| first_indexed | 2024-12-15T00:03:28Z |
| format | Article |
| id | doaj.art-6d5e3f822fb745eca6f2cbe1fbf38d5e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-15T00:03:28Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6d5e3f822fb745eca6f2cbe1fbf38d5e2022-12-21T22:42:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5525010.1371/journal.pone.0055250Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid.Olivier JalmarLiberty François-MoutalAna-Jesus García-SáezMark PerryThierry GranjonFrançois GonzalvezEyal GottliebJesus Ayala-SanmartinBeate KlösgenPetra SchwillePatrice X PetitCaspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23418437/?tool=EBI |
| spellingShingle | Olivier Jalmar Liberty François-Moutal Ana-Jesus García-Sáez Mark Perry Thierry Granjon François Gonzalvez Eyal Gottlieb Jesus Ayala-Sanmartin Beate Klösgen Petra Schwille Patrice X Petit Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid. PLoS ONE |
| title | Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid. |
| title_full | Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid. |
| title_fullStr | Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid. |
| title_full_unstemmed | Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid. |
| title_short | Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid. |
| title_sort | caspase 8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23418437/?tool=EBI |
| work_keys_str_mv | AT olivierjalmar caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT libertyfrancoismoutal caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT anajesusgarciasaez caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT markperry caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT thierrygranjon caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT francoisgonzalvez caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT eyalgottlieb caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT jesusayalasanmartin caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT beateklosgen caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT petraschwille caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid AT patricexpetit caspase8bindingtocardiolipiningiantunilamellarvesiclesprovidesafunctionaldockingplatformforbid |