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) to cause 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 ce...

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Autores principales: Reczek, Colleen R., Birsoy, Kıvanç, Kong, Hyewon, Martínez-Reyes, Inmaculada, Wang, Tim, Gao, Peng, Sabatini, David M., Chandel, Navdeep S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698099/
https://www.ncbi.nlm.nih.gov/pubmed/29058724
http://dx.doi.org/10.1038/nchembio.2499
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author Reczek, Colleen R.
Birsoy, Kıvanç
Kong, Hyewon
Martínez-Reyes, Inmaculada
Wang, Tim
Gao, Peng
Sabatini, David M.
Chandel, Navdeep S.
author_facet Reczek, Colleen R.
Birsoy, Kıvanç
Kong, Hyewon
Martínez-Reyes, Inmaculada
Wang, Tim
Gao, Peng
Sabatini, David M.
Chandel, Navdeep S.
author_sort Reczek, Colleen R.
collection PubMed
description Paraquat, a herbicide linked to Parkinson’s disease, generates reactive oxygen species (ROS) to cause 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 to uncover redox biology.
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spelling pubmed-56980992018-04-23 A CRISPR screen identifies a pathway required for paraquat-induced cell death Reczek, Colleen R. Birsoy, Kıvanç Kong, Hyewon Martínez-Reyes, Inmaculada Wang, Tim Gao, Peng Sabatini, David M. Chandel, Navdeep S. Nat Chem Biol Article Paraquat, a herbicide linked to Parkinson’s disease, generates reactive oxygen species (ROS) to cause 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 to uncover redox biology. 2017-10-23 2017-12 /pmc/articles/PMC5698099/ /pubmed/29058724 http://dx.doi.org/10.1038/nchembio.2499 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Reczek, Colleen R.
Birsoy, Kıvanç
Kong, Hyewon
Martínez-Reyes, Inmaculada
Wang, Tim
Gao, Peng
Sabatini, David M.
Chandel, Navdeep S.
A CRISPR screen identifies a pathway required for paraquat-induced cell death
title A CRISPR screen identifies a pathway required for paraquat-induced cell death
title_full A CRISPR screen identifies a pathway required for paraquat-induced cell death
title_fullStr A CRISPR screen identifies a pathway required for paraquat-induced cell death
title_full_unstemmed A CRISPR screen identifies a pathway required for paraquat-induced cell death
title_short A CRISPR screen identifies a pathway required for paraquat-induced cell death
title_sort crispr screen identifies a pathway required for paraquat-induced cell death
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698099/
https://www.ncbi.nlm.nih.gov/pubmed/29058724
http://dx.doi.org/10.1038/nchembio.2499
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