TY - JOUR
T1 - A CRISPR screen identifies a pathway required for paraquat-induced cell death
AU - Reczek, Colleen R.
AU - Birsoy, Kivanc
AU - Kong, Hyewon
AU - Martínez-Reyes, Inmaculada
AU - Wang, Tim
AU - Gao, Peng
AU - Sabatini, David M.
AU - Chandel, Navdeep S.
N1 - Funding Information:
We thank the Genome Technology Core of the Whitehead Institute for deep sequencing the genomic DNA samples. We thank the Flow Cytometry Core of Northwestern University for providing the BD LSRFortessa cell analyzer to assess cell viability. We are grateful to M.P. Murphy (University of Cambridge) for providing us MitoParaquat. This work was supported by a National Institute of Aging grant (5P01AG049665) to N.S.C. C.R.R. was supported by a National Institutes of Health postdoctoral training grant (T32 HL076139-11). H.K. was supported by a National Institutes of Health pre-doctoral training grant (T32 CA9560-30). K.B. was supported by grants from the National Institutes of Health (K22 CA1936600), a Searle Scholar Award, an Irma T. Hirschl/Monique Weill– Caulier Trust Award, and the Sidney Kimmel Foundation. D.M.S. is an investigator of the Howard Hughes Medical Institute.
Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nchembio.2499
DO - 10.1038/nchembio.2499
M3 - Article
C2 - 29058724
AN - SCOPUS:85034812710
SN - 1552-4450
VL - 13
SP - 1274
EP - 1279
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 12
ER -