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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Detalles Bibliográficos
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
Descripción
Sumario:[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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