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Comment
. 2022 Aug;19(8):867-868.
doi: 10.1038/s41423-022-00866-1. Epub 2022 Apr 22.

Cuproptosis: a new form of programmed cell death

Affiliations
Comment

Cuproptosis: a new form of programmed cell death

Yongqiang Wang et al. Cell Mol Immunol. 2022 Aug.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Schematic model of copper-induced cell death.
In cells that rely on mitochondrial respiration, copper binds to lipoylated DLAT after excessive accumulation due to ionophores or transporters, inducing aberrant oligomerization of DLAT and the formation of DLAT foci. Increased levels of insoluble DLAT causes cellularproteotoxic stress, which further induces cell death. FDX1 is involved in regulating the lipoylation of proteins. In addition, FDX1 reduces Cu(II) to Cu(I), resulting in the inhibition of Fe-S cluster synthesis, which in turn impairs the production of Fe-S cluster proteins.

Comment on

  • Copper induces cell death by targeting lipoylated TCA cycle proteins.
    Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, Rossen J, Joesch-Cohen L, Humeidi R, Spangler RD, Eaton JK, Frenkel E, Kocak M, Corsello SM, Lutsenko S, Kanarek N, Santagata S, Golub TR. Tsvetkov P, et al. Science. 2022 Mar 18;375(6586):1254-1261. doi: 10.1126/science.abf0529. Epub 2022 Mar 17. Science. 2022. PMID: 35298263 Free PMC article.

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. doi: 10.1126/science.abf0529. - DOI - PMC - PubMed
    1. Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 2020;21:85–100. doi: 10.1038/s41580-019-0173-8. - DOI - PubMed
    1. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–72. doi: 10.1016/j.cell.2012.03.042. - DOI - PMC - PubMed
    1. Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 2019;15:681–9. doi: 10.1038/s41589-019-0291-9. - DOI - PMC - PubMed
    1. Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, et al. The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med. 2012;52:2142–50. doi: 10.1016/j.freeradbiomed.2012.03.017. - DOI - PubMed

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