Journal
NATURE CHEMICAL BIOLOGY
Volume 13, Issue 12, Pages 1274-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2499
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Funding
- National Institute of Aging grant [5P01AG049665]
- National Institutes of Health postdoctoral training grant [T32 HL076139-11]
- Irma T. Hirschl/Monique Weill-Caulier Trust Award
- Sidney Kimmel Foundation
- National Institutes of Health pre-doctoral training grant [T32 C A9560-30]
- National institutes of Health [K22 CA1936600]
- Searle Scholar Award
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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 SLC4SA4 (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.
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