Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
Publ. Version/Full Text
Research data
DOI
 |
Open Access Gold |
|
as soon as is submitted to ZB.
GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling.
ACS Cent. Sci. 6, 41-53 (2020)
Ferroptosis is an iron-dependent form of regulated cell death linking iron, lipid, and glutathione levels to degenerative processes and tumor suppression. By performing a genome-wide activation screen, we identified a cohort of genes antagonizing ferroptotic cell death, including GTP cyclohydrolase-1 (GCH1) and its metabolic derivatives tetrahydrobiopterin/dihydrobiopterin (BH4/BH2). Synthesis of BH4/BH2 by GCH1-expressing cells caused lipid remodeling, suppressing ferroptosis by selectively preventing depletion of phospholipids with two polyunsaturated fatty acyl tails. GCH1 expression level in cancer cell lines stratified susceptibility to ferroptosis, in accordance with its expression in human tumor samples. The GCH1-BH4-phospholipid axis acts as a master regulator of ferroptosis resistance, controlling endogenous production of the antioxidant BH4, abundance of CoQ(10), and peroxidation of unusual phospholipids with two polyunsaturated fatty acyl tails. This demonstrates a unique mechanism of ferroptosis protection that is independent of the GPX4/glutathione system.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cell-death; Oxidative Stress; Tetrahydrobiopterin; Peroxidation; Activation; Mechanisms; Growth; Gch1; Bh4
ISSN (print) / ISBN
2374-7943
e-ISSN
2374-7951
Journal
ACS central science
Quellenangaben
Volume: 6,
Issue: 1,
Pages: 41-53
Publisher
ACS
Publishing Place
Washington, DC
Non-patent literature
Publications
Reviewing status
Peer reviewed