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Peter Tsvetkov, Shannon Coy, Boryana Petrova, Margaret B. Dreishpoon, Ana Verma, Mai Abdusamad, Jordan Rossen, Lena M. Joesch-Cohen, Ranad Humeidi, Ryan D. Spangler and 8 more
Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper induces cell death, however, is unknown. Here, we show in human cells that copper-dependent, regulated cell death is distinct from known death mechanisms and is dependent on mitochondrial respiration. We show that copper-dependent death occurs by means of direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle. This results in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, which leads to proteotoxic stress and ultimately cell death. These findings may explain the need for ancient copper homeostatic mechanisms.
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Tsvetkov, P., Coy, S., Petrova, B., Dreishpoon, M. B., Verma, A., Abdusamad, M., Rossen, J., Joesch-Cohen, L. M., Humeidi, R., Spangler, R. D., Eaton, J. K., Frenkel, E. M., Kocak, M., Corsello, S. M., Lutsenko, S., Kanarek, N., Santagata, S., & Golub, T. R. (2022). Copper induces cell death by targeting lipoylated TCA cycle proteins. Science, 375(6586), 1254–1261. https://doi.org/10.1126/science.abf0529
Tsvetkov, Peter, et al. "Copper induces cell death by targeting lipoylated TCA cycle proteins." Science, vol. 375, no. 6586, 2022, pp. 1254–1261, https://doi.org/10.1126/science.abf0529.
Tsvetkov, Peter, Shannon Coy, Boryana Petrova, Margaret B. Dreishpoon, Ana Verma, Mai Abdusamad, Jordan Rossen, et al. "Copper induces cell death by targeting lipoylated TCA cycle proteins." Science 375, no. 6586 (2022): 1254–1261. https://doi.org/10.1126/science.abf0529.
Tsvetkov P., Coy S., Petrova B. [и др.] Copper induces cell death by targeting lipoylated TCA cycle proteins // Science. — 2022. — Vol. 375, № 6586. — P. 1254–1261. — URL: https://doi.org/10.1126/science.abf0529
@article{tsvetkov2022copper,
title = {{Copper induces cell death by targeting lipoylated TCA cycle proteins}},
author = {Peter Tsvetkov and Shannon Coy and Boryana Petrova and Margaret B. Dreishpoon and Ana Verma and Mai Abdusamad and Jordan Rossen and Lena M. Joesch-Cohen and Ranad Humeidi and Ryan D. Spangler and John K. Eaton and Evgeni M. Frenkel and Mustafa Kocak and Steven M. Corsello and Svetlana Lutsenko and Naama Kanarek and Sandro Santagata and Todd R. Golub},
journal = {Science},
year = {2022},
volume = {375},
number = {6586},
pages = {1254--1261},
doi = {10.1126/science.abf0529},
url = {https://doi.org/10.1126/science.abf0529}
}TY - JOUR AU - Tsvetkov, Peter AU - Coy, Shannon AU - Petrova, Boryana AU - Dreishpoon, Margaret B. AU - Verma, Ana AU - Abdusamad, Mai AU - Rossen, Jordan AU - Joesch-Cohen, Lena M. AU - Humeidi, Ranad AU - Spangler, Ryan D. AU - Eaton, John K. AU - Frenkel, Evgeni M. AU - Kocak, Mustafa AU - Corsello, Steven M. AU - Lutsenko, Svetlana AU - Kanarek, Naama AU - Santagata, Sandro AU - Golub, Todd R. TI - Copper induces cell death by targeting lipoylated TCA cycle proteins JO - Science VL - 375 IS - 6586 SP - 1254 EP - 1261 PY - 2022 DA - 2022/03/17 DO - 10.1126/science.abf0529 UR - https://doi.org/10.1126/science.abf0529 ER -
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