The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
STING1 Promotes Ferroptosis Through MFN1/2-Dependent Mitochondrial Fusion
Open accessAbstract
Ferroptosis is a type of iron-dependent regulated cell death caused by the disruption that occurs when oxidative stress and antioxidant defenses interact, and then driven by lipid peroxidation and subsequent plasma membrane ruptures. The regulation of ferroptosis involves many factors, including the crosstalk between subcellular organelles, such as mitochondria, endoplasmic reticulum (ER), lysosomes, lipid droplets, and peroxisomes. Here, we show that the ER protein STING1 (also known as STING or TMEM173) promotes ferroptosis in human pancreatic cancer cell lines by increasing MFN1/2-dependent mitochondrial fusion, but not mitophagy-mediated mitochondrial removal. The classic ferroptosis inducer erastin, but not sulfasalazine, induces the accumulation of STING1 in the mitochondria, where it binds to MFN1/2 to trigger mitochondrial fusion, leading to subsequent reactive oxygen species production and lipid peroxidation. Consequently, in vitro or xenograft mouse models show that the genetic depletion of STING1 or MFN1/2 (but not the mitophagy regulator PINK1 or PRKN) reduces the sensitivity of pancreatic cancer cells to ferroptosis. These findings not only establish a new mitochondrial fusion-dependent cell death mechanism, but also indicate a potential strategy for enhancing ferroptosis-based therapy.
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Citations
Cites
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
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Self-citationFerroptosis: 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
Self-citationPINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835
Biological Functions of Autophagy Genes: A Disease Perspective
Levine, B., & Kroemer, G. (2019) · Cell · doi:10.1016/j.cell.2018.09.048 · Cited by 2,832
Autophagy promotes ferroptosis by degradation of ferritin
Hou, W., Xie, Y., Song, X., Sun, X., Lotze, M. T., Zeh, H. J., Kang, R., & Tang, D. (2016) · Autophagy · doi:10.1080/15548627.2016.1187366 · Cited by 2,332
Self-citationRole of Mitochondria in Ferroptosis
Gao, M., Yi, J., Zhu, J., Minikes, A. M., Monian, P., Thompson, C. B., & Jiang, X. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.10.042 · Cited by 2,120
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
Self-citationMitochondrial form and function
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“Mitochondria are dynamic membrane-bound organelles that are not only the main site of energy metabolism, but also participate in various cell signal transduction processes by regulating oxidative stress and calcium homeostasis (Friedman and Nunnari, 2014).”
BackgroundRAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels
Yagoda, N., von Rechenberg, M., Zaganjor, E., Bauer, A. J., Yang, W. S., Fridman, D. J., Wolpaw, A. J., Smukste, I., Peltier, J. M., Boniface, J. J., et al. (2007) · Nature · doi:10.1038/nature05859 · Cited by 1,631
Cited by
Signaling pathways and defense mechanisms of ferroptosis
Liu, J., Kang, R., & Tang, D. (2022) · The FEBS Journal · doi:10.1111/febs.16059 · Cited by 787
Self-citationGPX4 in cell death, autophagy, and disease
Xie, Y., Kang, R., Klionsky, D. J., & Tang, D. (2023) · Autophagy · doi:10.1080/15548627.2023.2218764 · Cited by 623
Self-citationThe interaction between ferroptosis and inflammatory signaling pathways
Chen, Y., Fang, Z.-M., Yi, X., Wei, X., & Jiang, D.-S. (2023) · Cell Death & Disease · doi:10.1038/s41419-023-05716-0 · Cited by 567
Organelle-specific regulation of ferroptosis
Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021) · Cell Death & Differentiation · doi:10.1038/s41418-021-00859-z · Cited by 398
Self-citationMitophagy and cGAS–STING crosstalk in neuroinflammation
Zhou, X., Wang, J., Yu, L., Qiao, G., Qin, D., Yuen-Kwan Law, B., Ren, F., Wu, J., & Wu, A. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.05.012 · Cited by 131
Metadata
- Authors
- Li, C., Liu, J., Hou, W., Kang, R., & Tang, D.
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2021-06-14
- Volume
- 9
- Pages
- 698679-698679
- ISSN
- 2296-634X (ISSN-L)
- OpenAlex
- W3166985228
- Cited by
- 180
- References
- 17
- FWCI
- 17.87
- Type
- journal article
- Language
- en
- Open access
- gold
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- Li, C., Liu, J., Hou, W., Kang, R., & Tang, D. (2021). STING1 Promotes Ferroptosis Through MFN1/2-Dependent Mitochondrial Fusion. Frontiers in Cell and Developmental Biology. https://doi.org/10.3389/fcell.2021.698679
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