A CRISPR screen identifies a pathway required for paraquat-induced cell death
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Paraquat, a herbicide linked to Parkinson's disease, generates reactive oxygen species (ROS), which causes cell death. Because the source of paraquat-induced ROS production remains unknown, we conducted a CRISPR-based positive-selection screen to identify metabolic genes essential for paraquat-induced cell death. Our screen uncovered three genes, POR (cytochrome P450 oxidoreductase), ATP7A (copper transporter), and SLC45A4 (sucrose transporter), required for paraquat-induced cell death. Furthermore, our results revealed POR as the source of paraquat-induced ROS production. Thus, our study highlights the use of functional genomic screens for uncovering redox biology.
Date issued
2017-10Department
Koch Institute for Integrative Cancer Research at MITJournal
Nature Chemical Biology
Publisher
Nature Publishing Group
Citation
Reczek, Colleen R, Kıvanç Birsoy, Hyewon Kong, Inmaculada Martínez-Reyes, Tim Wang, Peng Gao, David M Sabatini, and Navdeep S Chandel. “A CRISPR Screen Identifies a Pathway Required for Paraquat-Induced Cell Death.” Nature Chemical Biology 13, 12 (October 2017): 1274–1279 © 2017 Nature America, Inc., part of Springer Nature
Version: Author's final manuscript
ISSN
1552-4450
1552-4469