PuSH - Publication Server of Helmholtz Zentrum München

Friedmann Angeli, J.P.F.* ; Schneider, M.* ; Proneth, B. ; Tyurina, Y.Y.* ; Tyurin, V.A.* ; Hammond, V.J.* ; Herbach, N.* ; Aichler, M. ; Walch, A.K. ; Eggenhofer, E.* ; Basavarajappa, D.* ; Rådmark, O.* ; Kobayashi, S. ; Seibt, T. ; Beck, H.* ; Neff, F. ; Esposito, I.* ; Wanke, R.* ; Förster, H. ; Yefremova, O. ; Heinrichmeyer, M. ; Bornkamm, G.W. ; Geissler, E.K.* ; Thomas, S.B.* ; Stockwell, B.R.* ; O'Donnell, V.B.* ; Kagan, V.E.* ; Schick, J. ; Conrad, M.

Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice.

Nat. Cell Biol. 16, 1180-1191 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Ferroptosis is a non-apoptotic form of cell death induced by small molecules in specific tumour types, and in engineered cells overexpressing oncogenic RAS. Yet, its relevance in non-transformed cells and tissues is unexplored and remains enigmatic. Here, we provide direct genetic evidence that the knockout of glutathione peroxidase 4 (Gpx4) causes cell death in a pathologically relevant form of ferroptosis. Using inducible Gpx4(-/-) mice, we elucidate an essential role for the glutathione/Gpx4 axis in preventing lipid-oxidation-induced acute renal failure and associated death. We furthermore systematically evaluated a library of small molecules for possible ferroptosis inhibitors, leading to the discovery of a potent spiroquinoxalinamine derivative called Liproxstatin-1, which is able to suppress ferroptosis in cells, in Gpx4(-/-) mice, and in a pre-clinical model of ischaemia/reperfusion-induced hepatic damage. In sum, we demonstrate that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Journal Nature Cell Biology
Quellenangaben Volume: 16, Issue: 12, Pages: 1180-1191 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)