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A CRISPR screen identifies a pathway required for paraquat-induced cell death.

ABSTRACT: 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.

SUBMITTER: Reczek CR

PROVIDER: S-EPMC5698099 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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A CRISPR screen identifies a pathway required for paraquat-induced cell death.

Reczek Colleen R CR Birsoy Kıvanç K Kong Hyewon H Martínez-Reyes Inmaculada I Wang Tim T Gao Peng P Sabatini David M DM Chandel Navdeep S NS

Nature chemical biology 20171023 12

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. Furtherm ...[more]

PMID: 29058724

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