Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death

[Image: see text] Little is known about the regulation of nonapoptotic cell death. Using massive insertional mutagenesis of haploid KBM7 cells we identified nine genes involved in small-molecule-induced nonapoptotic cell death, including mediators of fatty acid metabolism (ACSL4) and lipid remodelin...

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Autores principales: Dixon, Scott J., Winter, Georg E., Musavi, Leila S., Lee, Eric D., Snijder, Berend, Rebsamen, Manuele, Superti-Furga, Giulio, Stockwell, Brent R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509420/
https://www.ncbi.nlm.nih.gov/pubmed/25965523
http://dx.doi.org/10.1021/acschembio.5b00245
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author Dixon, Scott J.
Winter, Georg E.
Musavi, Leila S.
Lee, Eric D.
Snijder, Berend
Rebsamen, Manuele
Superti-Furga, Giulio
Stockwell, Brent R.
author_facet Dixon, Scott J.
Winter, Georg E.
Musavi, Leila S.
Lee, Eric D.
Snijder, Berend
Rebsamen, Manuele
Superti-Furga, Giulio
Stockwell, Brent R.
author_sort Dixon, Scott J.
collection PubMed
description [Image: see text] Little is known about the regulation of nonapoptotic cell death. Using massive insertional mutagenesis of haploid KBM7 cells we identified nine genes involved in small-molecule-induced nonapoptotic cell death, including mediators of fatty acid metabolism (ACSL4) and lipid remodeling (LPCAT3) in ferroptosis. One novel compound, CIL56, triggered cell death dependent upon the rate-limiting de novo lipid synthetic enzyme ACC1. These results provide insight into the genetic regulation of cell death and highlight the central role of lipid metabolism in nonapoptotic cell death.
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spelling pubmed-45094202016-05-12 Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death Dixon, Scott J. Winter, Georg E. Musavi, Leila S. Lee, Eric D. Snijder, Berend Rebsamen, Manuele Superti-Furga, Giulio Stockwell, Brent R. ACS Chem Biol [Image: see text] Little is known about the regulation of nonapoptotic cell death. Using massive insertional mutagenesis of haploid KBM7 cells we identified nine genes involved in small-molecule-induced nonapoptotic cell death, including mediators of fatty acid metabolism (ACSL4) and lipid remodeling (LPCAT3) in ferroptosis. One novel compound, CIL56, triggered cell death dependent upon the rate-limiting de novo lipid synthetic enzyme ACC1. These results provide insight into the genetic regulation of cell death and highlight the central role of lipid metabolism in nonapoptotic cell death. American Chemical Society 2015-05-12 2015-07-17 /pmc/articles/PMC4509420/ /pubmed/25965523 http://dx.doi.org/10.1021/acschembio.5b00245 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Dixon, Scott J.
Winter, Georg E.
Musavi, Leila S.
Lee, Eric D.
Snijder, Berend
Rebsamen, Manuele
Superti-Furga, Giulio
Stockwell, Brent R.
Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
title Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
title_full Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
title_fullStr Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
title_full_unstemmed Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
title_short Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
title_sort human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509420/
https://www.ncbi.nlm.nih.gov/pubmed/25965523
http://dx.doi.org/10.1021/acschembio.5b00245
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