The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation
Open accessAbstract
AbstractFerroptosis is a non-apoptotic form of regulated cell death caused by the failure of the glutathione-dependent lipid-peroxide-scavenging network. FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. We investigated the mechanism and structural features necessary for ferroptosis initiation by FINO2. We found that FINO2 requires both an endoperoxide moiety and a nearby hydroxyl head group to initiate ferroptosis. In contrast to previously described ferroptosis inducers, FINO2 does not inhibit system xc– or directly target the reducing enzyme GPX4, as do erastin and RSL3, respectively, nor does it deplete GPX4 protein, as does FIN56. Instead, FINO2 both indirectly inhibits GPX4 enzymatic function and directly oxidizes iron, ultimately causing widespread lipid peroxidation. These findings suggest that endoperoxides such as FINO2 can initiate a multipronged mechanism of ferroptosis.FINO2 is a small molecule that requires the endoperoxide moiety and hydroxyl group to promote ferroptosis through indirect inhibition of GPX4 enzymatic function and direct oxidation of iron, resulting in increased lipid peroxidation.
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Cites
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Self-citationPeroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis
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Self-citationOxidized Redox State of Glutathione in the Endoplasmic Reticulum
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Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models
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“3, 12 Using an in vitro colorimetric assay, we monitored the oxidation state of iron treated with oxidizing compounds (Figure 5A).”
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“Unlike RSL3, FINO 2 did not cause a change in the HSQC spectrum of GPX4, indicating that FINO 2 is neither an allosteric nor active site ligand of GPX4 (Figure 3B and Supplementary Figure 6).”
InfluentialArtemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells
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Cited by
Targeting Ferroptosis as a Vulnerability in Cancer
Lei, G., Zhuang, L., & Gan, B. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00459-0 · Cited by 2,252
Ferroptosis: machinery and regulation
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099
Role of GPX4 in ferroptosis and its pharmacological implication
Seibt, T. M., Proneth, B., & Conrad, M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.014 · Cited by 1,520
Ferroptosis: Mechanisms and links with diseases
Yan, H.-F., Zou, T., Tuo, Q.-Z., Xu, S., Li, H., Belaidi, A. A., & Lei, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00428-9 · Cited by 1,471
The development of the concept of ferroptosis
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Metadata
- Authors
- Gaschler, M. M., Andia, A. A., Liu, H., Csuka, J. M., Hurlocker, B., Vaiana, C. A., Heindel, D. W., Zuckerman, D. S., Bos, P. H., Reznik, E., Ye, L. F., Tyurina, Y. Y., Lin, A. J., Shchepinov, M. S., Chan, A. Y., Peguero-Pereira, E., Fomich, M. A., Daniels, J. D., Bekish, A. V., Shmanai, V. V., Kagan, V. E., Mahal, L. K., Woerpel, K. A., & Stockwell, B. R.
- Venue
- Nature Chemical Biology
- Published
- 2018-04-02
- Volume
- 14
- Issue
- 5
- Pages
- 507-515
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2795028304
- Cited by
- 735
- References
- 10
- FWCI
- 37.37
- Type
- journal article
- Language
- en
- Open access
- green
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- Gaschler, M. M., Andia, A. A., Liu, H., Csuka, J. M., Hurlocker, B., Vaiana, C. A., Heindel, D. W., Zuckerman, D. S., Bos, P. H., Reznik, E., Ye, L. F., Tyurina, Y. Y., Lin, A. J., Shchepinov, M. S., Chan, A. Y., Peguero-Pereira, E., Fomich, M. A., Daniels, J. D., Bekish, A. V., . . . Stockwell, B. R. (2018). FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nature Chemical Biology. https://doi.org/10.1038/s41589-018-0031-6
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