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  Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway

Holze, C., Michaudel, C., Mackowiak, C., Haas, D. A., Benda, C., Hubel, P., et al. (2017). Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway. Nature Immunology. doi:10.1038/s41590-017-0013-y.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-7DF4-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-7DF5-0
Genre: Journal Article

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 Creators:
Holze, Cathleen1, Author              
Michaudel, Chloé2, Author
Mackowiak, Claire2, Author
Haas, Darya A.1, Author              
Benda, Christian3, Author              
Hubel, Philipp1, Author              
Pennemann, Friederike L.1, Author              
Schnepf, Daniel 2, Author
Wettmarshausen, Jennifer2, Author
Braun, Marianne4, Author              
Leung, Daisy W. 2, Author
Amarasinghe, Gaya K. 2, Author
Perocchi, Fabiana2, Author
Staeheli, Peter 2, Author
Ryffel, Bernhard 2, Author
Pichlmair, Andreas1, Author              
Affiliations:
1Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society, escidoc:1565166              
2External Organizations, escidoc:persistent22              
3Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, escidoc:1565144              
4Department: Systems and Computational Neurobiology / Borst, MPI of Neurobiology, Max Planck Society, escidoc:1113548              

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 Abstract: Reactive oxygen species (ROS) are generated by virus-infected cells; however, the physiological importance of ROS generated under these conditions is unclear. Here we found that the inflammation and cell death induced by exposure of mice or cells to sources of ROS were not altered in the absence of canonical ROS-sensing pathways or known cell-death pathways. ROS-induced cell-death signaling involved interactions among the cellular ROS sensor and antioxidant factor KEAP1, the phosphatase PGAM5 and the proapoptotic factor AIFM1. Pgam5–/– mice showed exacerbated lung inflammation and proinflammatory cytokines in an ozone-exposure model. Similarly, challenge with influenza A virus led to increased infiltration of the virus, lymphocytic bronchiolitis and reduced survival of Pgam5–/– mice. This pathway, which we have called ‘oxeiptosis’, was a ROS-sensitive, caspase independent, non-inflammatory cell-death pathway and was important for protection against inflammation induced by ROS or ROS-generating agents such as viral pathogens.

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 Dates: 2017-12-18
 Publication Status: Published online
 Pages: -
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 Rev. Method: -
 Identifiers: DOI: 10.1038/s41590-017-0013-y
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Project name: European Research Council (starting grant ERC-StG iVIP, 311339) German research foundation (PI 1084/2 and TRR179 to A.P.)
Grant ID: 311339
Funding program: ERC-StG iVIP
Funding organization: European Research Council

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Title: Nature Immunology
  Other : Nat. Immunol.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America Inc.
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1529-2908
CoNE: http://pubman.mpdl.mpg.de/cone/journals/resource/974392607073