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

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.

• Authors: Cathleen Holze, Chloé Michaudel, Claire Mackowiak, Darya A Haas, Christian Benda, Philipp Hubel, Friederike L Pennemann, Daniel Schnepf, Jennifer Wettmarshausen, Marianne Braun, Daisy W Leung, Gaya K Amarasinghe, Fabiana Perocchi, Peter Staeheli, Bernhard Ryffel, Andreas Pichlmair
• Journal: Nature immunology (Nat Immunol) Vol. 19 Issue 2 Pg. 130-140 (02 2018) ISSN: 1529-2916 [Electronic] United States
• PMID: 29255269 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AIFM1 protein, human
• Apoptosis Inducing Factor
• Kelch-Like ECH-Associated Protein 1
• Mitochondrial Proteins
• Reactive Oxygen Species
• PGAM5 protein, human
• PGAM5 protein, mouse
• Phosphoprotein Phosphatases

Topics

• Animals
• Apoptosis Inducing Factor (metabolism)
• Cell Death (physiology)
• Humans
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Mice
• Mice, Knockout
• Mitochondrial Proteins (metabolism)
• Phosphoprotein Phosphatases (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (physiology)