The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation
Open accessAbstract
Ferroptosis is a form of regulated non-apoptotic cell death that has been implicated in several disease contexts. A better understanding of the ferroptotic death mechanism could lead to the development of new therapeutics for degenerative diseases, and a better understanding of how to induce ferroptosis in specific tumor contexts. We performed an unbiased genome-wide siRNA screen to find genetic suppressors of ferroptosis. We determined that loss of CARS, the cysteinyl-tRNA synthetase, suppresses ferroptosis induced by erastin, which inhibits the cystine–glutamate antiporter known as system xc−. Knockdown of CARS inhibited erastin-induced death by preventing the induction of lipid reactive oxygen species, without altering iron homeostasis. Knockdown of CARS led to the accumulation of cystathionine, a metabolite on the transsulfuration pathway, and upregulated genes associated with serine biosynthesis and transsulfuration. In addition, inhibition of the transsulfuration pathway resensitized cells to erastin, even after CARS knockdown. These studies demonstrate a new mechanism of resistance to ferroptosis and may lead to strategies for inducing and suppressing ferroptosis in diverse contexts.
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Citations
Cites
Regulation of Ferroptotic Cancer Cell Death by GPX4
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Self-citationInactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Self-citationCreation of human tumour cells with defined genetic elements
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Self-citationRAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels
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Self-citationFerrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models
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“in models of glutamate toxicity, raising the question of whether CARS knockdown could prevent glutamate toxicity.(4,12) To test whether CARS knockdown could prevent glutamate toxicity in a high-throughput format, we developed an assay”
BackgroundSelf-citationIntegrated Stress Response Modulates Cellular Redox State via Induction of Cystathionine γ-Lyase
Dickhout, J. G., Carlisle, R. E., Jerome, D. E., Mohammed-Ali, Z., Jiang, H., Yang, G., Mani, S., Garg, S. K., Banerjee, R., Kaufman, R. J., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.304576 · Cited by 129
Cited by
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
Self-citationGalluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2239 · Cited by 4,293
The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
Bersuker, K., Hendricks, J. M., Li, Z., Magtanong, L., Ford, B., Tang, P. H., Roberts, M. A., Tong, B., Maimone, T. J., Zoncu, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1705-2 · Cited by 3,703
Ferroptosis: process and function
Xie, Y., Hou, W., Song, X., Yu, Y., Huang, J., Sun, X., Kang, R., & Tang, D. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.158 · Cited by 3,727
Metadata
- Authors
- Hayano, M., Yang, W. S., Corn, C. K., Pagano, N. C., & Stockwell, B. R.
- Venue
- Cell Death & Differentiation
- Published
- 2015-07-17
- Volume
- 23
- Issue
- 2
- Pages
- 270-278
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1798710600
- Cited by
- 457
- References
- 9
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hayano, M., Yang, W. S., Corn, C. K., Pagano, N. C., & Stockwell, B. R. (2016). Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death & Differentiation. https://doi.org/10.1038/cdd.2015.93
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