A CRISPR screen identifies a pathway required for paraquat-induced cell death.
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.
|Year of Publication||
Nat Chem Biol
|PubMed Central ID||
K22 CA193660 / CA / NCI NIH HHS / United States
T32 CA009560 / CA / NCI NIH HHS / United States
P01 AG049665 / AG / NIA NIH HHS / United States
R35 CA197532 / CA / NCI NIH HHS / United States
T32 HL076139 / HL / NHLBI NIH HHS / United States