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Cuproptosis: a new form of programmed cell death

Cellular & Molecular Immunology volume 19, pages 867–868 (2022)Cite this article

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A recent study by Tsvetkov et al. was published in Science and proposed a novel form of copper-induced cell death. Tsvetkov et al. revealed that excess intracellular copper induces the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), which is associated with the mitochondrial tricarboxylic acid (TCA) cycle, resulting in proteotoxic stress and leading to a novel form of cell death termed cuproptosis [1].

Previous studies have reported several types of precisely regulated programmed cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis [2]. Dixon et al. revealed that ferroptosis is a form of programmed cell death involving a series of unique morphological and biochemical features, including mitochondrial shrinkage and the accumulation of reactive oxygen species (ROS) [3]. Similar to iron, copper is an intracellular trace metal that plays an indispensable role in maintaining the function of proteins. Excessive copper can lead to cytotoxicity, but the exact mechanism is still unclear [4]. Tsvetkov et al. found that elesclomol, a copper ionophore that was first used to treat cancer, killed cells when loaded with copper, whereas elesclomol alone did not induce cell death, suggesting that cell death was caused by copper toxicity.

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Fig. 1: Schematic model of copper-induced cell death.

References

  1. Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375:1254–61. https://doi.org/10.1126/science.abf0529

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Acknowledgements

This work was supported by a special program from the Ministry of Science and Technology of China (2021YFA101000), the Chinese National Natural Science Funds (U20A20393, U20A201376, 31925013, 3212500161, 82041009, 31871405, 31701234, 81902947, 82041009, 31671457, 31571460 and 91753139), the Jiangsu Provincial Distinguished Young Scholars Award (BK20180043), the Key Project of the University Natural Science Foundation of Jiangsu Province (19KJA550003), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_2036).

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Authors and Affiliations

  1. Institutes of Biology and Medical Science, Soochow University, Suzhou, 215123, China

    Yongqiang Wang & Fangfang Zhou

  2. MOE Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China

    Long Zhang

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Correspondence to Long Zhang or Fangfang Zhou.

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Wang, Y., Zhang, L. & Zhou, F. Cuproptosis: a new form of programmed cell death. Cell Mol Immunol 19, 867–868 (2022). https://doi.org/10.1038/s41423-022-00866-1

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