Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
AI Summary:
Mitochondrial outer membrane permeabilisation (MOMP) is a crucial step in apoptosis, allowing cytochrome c release and subsequent caspase activation. However, MOMP has also been shown to be pro-inflammatory, triggering NF-B signalling and potentially leading to anti-tumour immunity.AI Topics:
Mitochondrial outer membrane permeabilisation (MOMP) is often essential for apoptosis, by enabling cytochrome c release that leads to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory with emerging cellular roles, including its ability to elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell regulates this remains poorly defined. We find that upon MOMP, many proteins localised either to inner or outer mitochondrial membranes are ubiquitylated in a promiscuous manner. This extensive ubiquitylation serves to recruit the essential adaptor molecule NEMO, leading to the activation of pro-inflammatory NF-κB signalling. We show that disruption of mitochondrial outer membrane integrity through different means leads to the engagement of a similar pro-inflammatory signalling platform. Therefore, mitochondrial integrity directly controls inflammation, such that permeabilised mitochondria initiate NF-κB signalling.
Vringer, Esmee
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listHeilig, Rosalie
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listRiley, Joel S.
Author
von Mässenhausen, Anne and Schlecht, Marlena Nastassja and Beer, Kristina and Maremonti, Francesca and Tonnus, Wulf and Belavgeni, Alexia and Gavali, Shubhangi and Flade, Karolin and Riley, Joel S. and Zamora Gonzalez, Nadia and Brucker, Anne and Becker, Jorunn Naila and Tmava, Mirela and Meyer, Claudia and Peitzsch, Mirko and Hugo, Christian and Gembardt, Florian and Angeli, Jose Pedro Friedmann and Bornstein, Stefan R. and Tait, Stephen W. G. and Linkermann, Andreas (2024) Treatment with siRNAs is commonly associated with GPX4 up-regulation and target knockdown-independent sensitization to ferroptosis. Science Advances, 10 (11): eadk7329. ISSN 2375-2548
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
Victorelli, Stella and Salmonowicz, Hanna and Chapman, James and Martini, Helene and Vizioli, Maria Grazia and Riley, Joel S. and Cloix, Catherine and Hall-Younger, Ella and Espindola-Netto, Jair Machado and Jurk, Diana and Lagnado, Anthony B. and Gomez, Lilian Sales and Farr, Joshua N. and Saul, Dominik and Reed, Rebecca and Kelly, George and Eppard, Madeline and Greaves, Laura C. and Dou, Zhixun and Pirius, Nicholas and Szczepanowska, Karolina and Porritt, Rebecca A. and Huang, Huijie and Huang, Timothy Y. and Mann, Derek A. and Masuda, Claudio Akio and Khosla, Sundeep and Dai, Haiming and Kaufmann, Scott H. and Zacharioudakis, Emmanouil and Gavathiotis, Evripidis and LeBrasseur, Nathan K. and Lei, Xue and Sainz, Alva G. and Korolchuk, Viktor I. and Adams, Peter D. and Shadel, Gerald S. and Tait, Stephen W.G. and Passos, João F. (2023) Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature, 622 (7983). pp. 627-636. ISSN 0028-0836
See full publications listBlack, Annabel
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listCloix, Catherine
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
Victorelli, Stella and Salmonowicz, Hanna and Chapman, James and Martini, Helene and Vizioli, Maria Grazia and Riley, Joel S. and Cloix, Catherine and Hall-Younger, Ella and Espindola-Netto, Jair Machado and Jurk, Diana and Lagnado, Anthony B. and Gomez, Lilian Sales and Farr, Joshua N. and Saul, Dominik and Reed, Rebecca and Kelly, George and Eppard, Madeline and Greaves, Laura C. and Dou, Zhixun and Pirius, Nicholas and Szczepanowska, Karolina and Porritt, Rebecca A. and Huang, Huijie and Huang, Timothy Y. and Mann, Derek A. and Masuda, Claudio Akio and Khosla, Sundeep and Dai, Haiming and Kaufmann, Scott H. and Zacharioudakis, Emmanouil and Gavathiotis, Evripidis and LeBrasseur, Nathan K. and Lei, Xue and Sainz, Alva G. and Korolchuk, Viktor I. and Adams, Peter D. and Shadel, Gerald S. and Tait, Stephen W.G. and Passos, João F. (2023) Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature, 622 (7983). pp. 627-636. ISSN 0028-0836
See full publications listSkalka, George L.
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
Skalka, George L. and Tsakovska, Mina and Murphy, Daniel (2024) Kinase signaling adaptation supports dysfunctional mitochondria in disease. Frontiers in Molecular Biosciences, 11: 1354682. ISSN 2296-889X
See full publications listMontes-Gómez, Alfredo E.
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listAguado, Aurore
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listLilla, Sergio
Author
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listWalczak, Henning
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listGyrd-Hansen, Mads
Author
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listMurphy, Daniel
Author
Vincelette, Nicole D. and Yu, Xiaoqing and Kuykendall, Andrew T. and Moon, Jungwon and Su, Siyuan and Cheng, Chia- Ho and Sammut, Rinzine and Razabdouski, Tiffany N. and Nguyen, Hai Vu and Eksioglu, Erika A. and Chan, Onyee and Al Ali, Najla and Patel, Parth C. and Lee, Dae Hyun and Nakanishi, Shima and Ferreira, Renan B. and Mo, Qianxing and Cory, Suzanne and Lawrence, Harshani R. and Zhang, Ling and Murphy, Daniel J. and Komrokji, Rami S. and Lee, Daesung and Kaufmann, Scott H. and Cleveland, John L. and Yun, Seongseok (2024) Trisomy 8 defines a distinct subtype of myeloproliferative neoplasms driven by the MYC-alarmin axis. Blood Cancer Discovery, 5 (4). pp. 276-297. ISSN 2643-3230
Murphy, Daniel J. (2024) Investigating lung cancer using genetically engineered mouse models (GEMMS). Open Access Government, 42 (1). pp. 112-113. ISSN 2516-3817
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listHuang, Danny T.
Author
Vosbein, Pernille and Vergara, Paula Paredes and Huang, Danny T. and Thomson, Andrew R. (2024) An engineered ubiquitin binding coiled coil peptide. Chemical Science, 15 (38). pp. 15776-15782. ISSN 2041-6520
Bohlen, Jonathan and Bagarić, Ivan and Vatovec, Taja and Ogishi, Masato and Ahmed, Syed F. and Cederholm, Axel and Buetow, Lori and Sobrino, Steicy and Le Floc’h, Corentin and Arango-Franco, Carlos A. and Seabra, Luis and Michelet, Marine and Barzaghi, Federica and Leardini, Davide and Saettini, Francesco and Vendemini, Francesca and Baccelli, Francesco and Catala, Albert and Gambineri, Eleonora and Veltroni, Marinella and Aguilar de la Red, Yurena and Rice, Gillian I. and Consonni, Filippo and Berteloot, Laureline and Largeaud, Laetitia and Conti, Francesca and Roullion, Cécile and Masson, Cécile and Bessot, Boris and Seeleuthner, Yoann and Le Voyer, Tom and Rinchai, Darawan and Rosain, Jérémie and Neehus, Anna-Lena and Erazo-Borrás, Lucia and Li, Hailun and Janda, Zarah and Cho, En-Jui and Muratore, Edoardo and Soudée, Camille and Lainé, Candice and Delabesse, Eric and Goulvestre, Claire and Ma, Cindy S. and Puel, Anne and Tangye, Stuart G. and André, Isabelle and Bole-Feysot, Christine and Abel, Laurent and Erlacher, Miriam and Zhang, Shen-Ying and Béziat, Vivien and Lagresle-Peyrou, Chantal and Six, Emmanuelle and Pasquet, Marlène and Alsina, Laia and Aiuti, Alessandro and Zhang, Peng and Crow, Yanick J. and Landegren, Nils and Masetti, Riccardo and Huang, Danny T. and Casanova, Jean-Laurent and Bustamante, Jacinta (2024) Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation. Journal of Clinical Investigation, 134 (20): e181604. ISSN 0021-9738
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
See full publications listZanivan, Sara
Author
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listTait, Stephen W.G.
Author
Hall-Younger, Ella and Tait, Stephen W.G. (2025) Mitochondria and cell death signalling. Current Opinion in Cell Biology, 94: 102510. ISSN 0955-0674
Ahmed Hassan Elshiekh, Asma and Tait, Stephen W.G. (2024) Tumour immunogenicity goes with the (mitochondrial electron) flow. Molecular Oncology, 18 (5). pp. 1054-1057. ISSN 1574-7891
Vringer, Esmee and Heilig, Rosalie and Riley, Joel S. and Black, Annabel and Cloix, Catherine and Skalka, George and Montes-Gómez, Alfredo E. and Aguado, Aurore and Lilla, Sergio and Walczak, Henning and Gyrd-Hansen, Mads and Murphy, Daniel J. and Huang, Danny T. and Zanivan, Sara and Tait, Stephen W.G. (2024) Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO Journal, 43 (6). pp. 904-930. ISSN 0261-4189
See full publications listAvailable under License Creative Commons Attribution.
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