PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
20.058
3.516
966
1110
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Zeitschrift Nature Cell Biology
Quellenangaben Band: 16, Heft: 12, Seiten: 1180-1191 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies

Immune Response and Infection
PSP-Element(e) G-500500-004
G-500500-001
G-500390-001
G-500300-001
G-508100-005
G-501400-006
G-501490-001
PubMed ID 25402683
DOI 10.1038/ncb3064
WOS ID WOS:000345777300009
Scopus ID 84925286831
Erfassungsdatum 2014-11-19
[➜Korrektur melden]