Ferroptosis spreads to neighboring cells via plasma membrane contacts
Abstract Ferroptosis is a lytic, iron-dependent form of regulated cell death characterized by excessive lipid peroxidation and associated with necrosis spread in diseased tissues through unknown mechanisms. Using a novel optogenetic system for light-driven ferroptosis induction via degradation of th...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58175-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850208751876833280 |
|---|---|
| author | Bernhard F. Roeck Sara Lotfipour Nasudivar Michael R. H. Vorndran Lena Schueller F. Isil Yapici Matthias Rübsam Silvia von Karstedt Carien M. Niessen Ana J. Garcia-Saez |
| author_facet | Bernhard F. Roeck Sara Lotfipour Nasudivar Michael R. H. Vorndran Lena Schueller F. Isil Yapici Matthias Rübsam Silvia von Karstedt Carien M. Niessen Ana J. Garcia-Saez |
| author_sort | Bernhard F. Roeck |
| collection | DOAJ |
| description | Abstract Ferroptosis is a lytic, iron-dependent form of regulated cell death characterized by excessive lipid peroxidation and associated with necrosis spread in diseased tissues through unknown mechanisms. Using a novel optogenetic system for light-driven ferroptosis induction via degradation of the anti-ferroptotic protein GPX4, we show that lipid peroxidation and ferroptotic death can spread to neighboring cells through their closely adjacent plasma membranes. Ferroptosis propagation is dependent on cell distance and completely abolished by disruption of α-catenin-dependent intercellular contacts or by chelation of extracellular iron. Remarkably, bridging cells with a lipid bilayer or increasing contacts between neighboring cells enhances ferroptosis spread. Reconstitution of iron-dependent spread of lipid peroxidation between pure lipid, contacting liposomes provides evidence for the physicochemical mechanism involved. Our findings support a model in which iron-dependent lipid peroxidation propagates across proximal plasma membranes of neighboring cells, thereby promoting the transmission of ferroptotic cell death with consequences for pathological tissue necrosis spread. |
| format | Article |
| id | doaj-art-192407955e544abcbc15bef4eca2e0b6 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-192407955e544abcbc15bef4eca2e0b62025-08-20T02:10:10ZengNature PortfolioNature Communications2041-17232025-03-0116111810.1038/s41467-025-58175-wFerroptosis spreads to neighboring cells via plasma membrane contactsBernhard F. Roeck0Sara Lotfipour Nasudivar1Michael R. H. Vorndran2Lena Schueller3F. Isil Yapici4Matthias Rübsam5Silvia von Karstedt6Carien M. Niessen7Ana J. Garcia-Saez8Institute for Genetics, University of CologneInstitute for Genetics, University of CologneInstitute for Genetics, University of CologneInstitute for Genetics, University of CologneCECAD Cluster of Excellence, University of CologneCECAD Cluster of Excellence, University of CologneCECAD Cluster of Excellence, University of CologneCECAD Cluster of Excellence, University of CologneInstitute for Genetics, University of CologneAbstract Ferroptosis is a lytic, iron-dependent form of regulated cell death characterized by excessive lipid peroxidation and associated with necrosis spread in diseased tissues through unknown mechanisms. Using a novel optogenetic system for light-driven ferroptosis induction via degradation of the anti-ferroptotic protein GPX4, we show that lipid peroxidation and ferroptotic death can spread to neighboring cells through their closely adjacent plasma membranes. Ferroptosis propagation is dependent on cell distance and completely abolished by disruption of α-catenin-dependent intercellular contacts or by chelation of extracellular iron. Remarkably, bridging cells with a lipid bilayer or increasing contacts between neighboring cells enhances ferroptosis spread. Reconstitution of iron-dependent spread of lipid peroxidation between pure lipid, contacting liposomes provides evidence for the physicochemical mechanism involved. Our findings support a model in which iron-dependent lipid peroxidation propagates across proximal plasma membranes of neighboring cells, thereby promoting the transmission of ferroptotic cell death with consequences for pathological tissue necrosis spread.https://doi.org/10.1038/s41467-025-58175-w |
| spellingShingle | Bernhard F. Roeck Sara Lotfipour Nasudivar Michael R. H. Vorndran Lena Schueller F. Isil Yapici Matthias Rübsam Silvia von Karstedt Carien M. Niessen Ana J. Garcia-Saez Ferroptosis spreads to neighboring cells via plasma membrane contacts Nature Communications |
| title | Ferroptosis spreads to neighboring cells via plasma membrane contacts |
| title_full | Ferroptosis spreads to neighboring cells via plasma membrane contacts |
| title_fullStr | Ferroptosis spreads to neighboring cells via plasma membrane contacts |
| title_full_unstemmed | Ferroptosis spreads to neighboring cells via plasma membrane contacts |
| title_short | Ferroptosis spreads to neighboring cells via plasma membrane contacts |
| title_sort | ferroptosis spreads to neighboring cells via plasma membrane contacts |
| url | https://doi.org/10.1038/s41467-025-58175-w |
| work_keys_str_mv | AT bernhardfroeck ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT saralotfipournasudivar ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT michaelrhvorndran ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT lenaschueller ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT fisilyapici ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT matthiasrubsam ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT silviavonkarstedt ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT carienmniessen ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts AT anajgarciasaez ferroptosisspreadstoneighboringcellsviaplasmamembranecontacts |