Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death
By Scott J. Dixon, Georg E. Winter, Leila Musavi, Eric D. Lee, B. Snijder, Manuele Rebsamen, G. Superti‐Furga, Brent R. Stockwell. ACS Chemical Biology, 2015
943 citations recorded by the source corpus.
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.
Subfields: Epidemiology, Immunology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/12a4ddda2b9b853dae1abaf0865c5ed2c434d8ad
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Citations in the corpus
- Molecular mechanisms of cell death in neurological diseases (2021, background): “Many molecular components of ferroptosis have been identified, including ACSL4 and LPCAT3 that generate the membrane lipids susceptible to peroxidation [103, 104], and the glutamate-cystine antiporter system xCT required to supply cysteine to the cell.”
- Transferrin Receptor Is a Specific Ferroptosis Marker (2020, neutral): “Acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4) was found to be required for ferroptotic cell death (Dixon et al., 2015; Doll et al., 2017; Yuan et al., 2016).”
- Exogenous Monounsaturated Fatty Acids Promote a Ferroptosis-Resistant Cell State (2019, positive): “The role of ACSL4 in the protective effects of exogenous MUFAs could not be determined, as deletion of this protein made cells insensitive to erastin2, consistent with recent reports (Dixon et al., 2015; Doll et al., 2017; Kagan et al., 2017) (Figure 5A).”
- CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4 (2022, background): “ACSL4 preferentially uses PUFAs, including arachidonic acid, as substrates (Dixon et al., 2015; Doll et al., 2017).”
- Identification of ACSL4 as a biomarker and contributor of ferroptosis. (2016, result): “These results are consistent with the findings from the previous haploid genetic screening showing that ACSL4 is upregulated in RSL3-induced ferroptosis in the human myeloid leukemia cell line KBM7 [26].”