Ferroptosis Detection: From Approaches to Applications
Fantian Zeng
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
These authors contributed equally to this work.
Contribution: Conceptualization (equal), Writing - original draft (equal)
Search for more papers by this authorSureya Nijiati
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
These authors contributed equally to this work.
Contribution: Conceptualization (equal), Writing - original draft (equal)
Search for more papers by this authorLongguang Tang
Affiliated Gaozhou People's Hospital, Guangdong Medical University, Guangdong, 524023 China
These authors contributed equally to this work.
Contribution: Writing - original draft (supporting)
Search for more papers by this authorJinmin Ye
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
Contribution: Writing - original draft (supporting)
Search for more papers by this authorCorresponding Author
Zijian Zhou
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
Shenzhen Research Institute of Xiamen University, Shenzhen, 518057 China
Contribution: Funding acquisition (lead), Supervision (lead), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Xiaoyuan Chen
Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074 Singapore
Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599 Singapore
Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597 Singapore
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673 Singapore
Contribution: Funding acquisition (supporting), Supervision (supporting), Writing - review & editing (equal)
Search for more papers by this authorFantian Zeng
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
These authors contributed equally to this work.
Contribution: Conceptualization (equal), Writing - original draft (equal)
Search for more papers by this authorSureya Nijiati
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
These authors contributed equally to this work.
Contribution: Conceptualization (equal), Writing - original draft (equal)
Search for more papers by this authorLongguang Tang
Affiliated Gaozhou People's Hospital, Guangdong Medical University, Guangdong, 524023 China
These authors contributed equally to this work.
Contribution: Writing - original draft (supporting)
Search for more papers by this authorJinmin Ye
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
Contribution: Writing - original draft (supporting)
Search for more papers by this authorCorresponding Author
Zijian Zhou
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102 China
Shenzhen Research Institute of Xiamen University, Shenzhen, 518057 China
Contribution: Funding acquisition (lead), Supervision (lead), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Xiaoyuan Chen
Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074 Singapore
Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599 Singapore
Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597 Singapore
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673 Singapore
Contribution: Funding acquisition (supporting), Supervision (supporting), Writing - review & editing (equal)
Search for more papers by this authorGraphical Abstract
We systematically summarize the ferroptosis detection approaches for subcellular organelles, biological events, and chemical markers, providing a multi-scale perspective on the regulation of the molecular machinery of ferroptosis. Moreover, we highlight the potential of advanced applications that integrate ferroptosis detection techniques with multifunctional platforms. The development of these applications holds great promise in promoting the transition of ferroptosis research from bench to bedside.
Abstract
Understanding the intricate molecular machinery that governs ferroptosis and leveraging this accumulating knowledge could facilitate disease prevention, diagnosis, treatment, and prognosis. Emerging approaches for the in situ detection of the major regulators and biological events across cellular, tissue, and in living subjects provide a multiscale perspective for studying ferroptosis. Furthermore, advanced applications that integrate ferroptosis detection and the latest technologies hold tremendous promise in ferroptosis research. In this review, we first briefly summarize the mechanisms and key regulators underlying ferroptosis. Ferroptosis detection approaches are then presented to delineate their design, mechanisms of action, and applications. Special interest is placed on advanced ferroptosis applications that integrate multifunctional platforms. Finally, we discuss the prospects and challenges of ferroptosis detection approaches and applications, with the aim of providing a roadmap for the theranostic development of a broad range of ferroptosis-related diseases.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
References
- 1
- 1aD. Tang, R. Kang, T. V. Berghe, P. Vandenabeele, G. Kroemer, Cell Res. 2019, 29, 347–364;
- 1bF. Peng, M. Liao, R. Qin, S. Zhu, C. Peng, L. Fu, Y. Chen, B. Han, Signal Transduction Targeted Ther. 2022, 7, 286.
- 2E. Koren, Y. Fuchs, Cancer Discovery 2021, 11, 245–265.
- 3S. J. Dixon, K. M. Lemberg, M. R. Lamprecht, R. Skouta, E. M. Zaitsev, C. E. Gleason, D. N. Patel, A. J. Bauer, A. M. Cantley, W. S. Yang, B. Morrison 3rd, B. R. Stockwell, Cell 2012, 149, 1060–1072.
- 4
- 4aM. J. Hangauer, V. S. Viswanathan, M. J. Ryan, D. Bole, J. K. Eaton, A. Matov, J. Galeas, H. D. Dhruv, M. E. Berens, S. L. Schreiber, F. McCormick, M. T. McManus, Nature 2017, 551, 247–250;
- 4bJ. Tsoi, L. Robert, K. Paraiso, C. Galvan, K. M. Sheu, J. Lay, D. J. L. Wong, M. Atefi, R. Shirazi, X. Wang, D. Braas, C. S. Grasso, N. Palaskas, A. Ribas, T. G. Graeber, Cancer Cell 2018, 33, 890–904.e5;
- 4cL. Magtanong, P. J. Ko, M. To, J. Y. Cao, G. C. Forcina, A. Tarangelo, C. C. Ward, K. Cho, G. J. Patti, D. K. Nomura, J. A. Olzmann, S. J. Dixon, Cell Chem. Biol. 2019, 26, 420–432.e9;
- 4dJ. L. Roh, E. H. Kim, H. J. Jang, J. Y. Park, D. Shin, Cancer Lett. 2016, 381, 96–103;
- 4eJ. Wu, A. M. Minikes, M. Gao, H. Bian, Y. Li, B. R. Stockwell, Z. N. Chen, X. Jiang, Nature 2019, 572, 402–406.
- 5
- 5aV. S. Viswanathan, M. J. Ryan, H. D. Dhruv, S. Gill, O. M. Eichhoff, B. Seashore-Ludlow, S. D. Kaffenberger, J. K. Eaton, K. Shimada, A. J. Aguirre, S. R. Viswanathan, S. Chattopadhyay, P. Tamayo, W. S. Yang, M. G. Rees, S. Chen, Z. V. Boskovic, S. Javaid, C. Huang, X. Wu, Y. Y. Tseng, E. M. Roider, D. Gao, J. M. Cleary, B. M. Wolpin, J. P. Mesirov, D. A. Haber, J. A. Engelman, J. S. Boehm, J. D. Kotz, C. S. Hon, Y. Chen, W. C. Hahn, M. P. Levesque, J. G. Doench, M. E. Berens, A. F. Shamji, P. A. Clemons, B. R. Stockwell, S. L. Schreiber, Nature 2017, 547, 453–457;
- 5bY. Zou, W. S. Henry, E. L. Ricq, E. T. Graham, V. V. Phadnis, P. Maretich, S. Paradkar, N. Boehnke, A. A. Deik, F. Reinhardt, J. K. Eaton, B. Ferguson, W. Wang, J. Fairman, H. R. Keys, V. Dančík, C. B. Clish, P. A. Clemons, P. T. Hammond, L. A. Boyer, R. A. Weinberg, S. L. Schreiber, Nature 2020, 585, 603–608;
- 5cI. Poursaitidis, X. Wang, T. Crighton, C. Labuschagne, D. Mason, S. L. Cramer, K. Triplett, R. Roy, O. E. Pardo, M. J. Seckl, S. W. Rowlinson, E. Stone, R. F. Lamb, Cell Rep. 2017, 18, 2547–2556.
- 6
- 6aT. X. Wang, J. Y. Liang, C. Zhang, Y. Xiong, K. L. Guan, H. X. Yuan, Cell Death Dis. 2019, 10, 755;
- 6bX. Luo, H. B. Gong, H. Y. Gao, Y. P. Wu, W. Y. Sun, Z. Q. Li, G. Wang, B. Liu, L. Liang, H. Kurihara, W. J. Duan, Y. F. Li, R. R. He, Cell Death Differ. 2021, 28, 1971–1989.
- 7Y. Mi, X. Gao, H. Xu, Y. Cui, Y. Zhang, X. Gou, Neuromol. Med. 2019, 21, 110–119.
- 8W. D. Bao, P. Pang, X. T. Zhou, F. Hu, W. Xiong, K. Chen, J. Wang, F. Wang, D. Xie, Y. Z. Hu, Z. T. Han, H. H. Zhang, W. X. Wang, P. T. Nelson, J. G. Chen, Y. Lu, H. Y. Man, D. Liu, L. Q. Zhu, Cell Death Differ. 2021, 28, 1548–1562.
- 9H. Y. Zhu, Q. J. He, B. Yang, J. Cao, Acta Pharm. Sin. 2021, 42, 1379–1381.
- 10T. Wang, D. Tomas, N. D. Perera, B. Cuic, S. Luikinga, A. Viden, S. K. Barton, C. A. McLean, A. L. Samson, A. Southon, A. I. Bush, J. M. Murphy, B. J. Turner, Cell Death Differ. 2022, 29, 1187–1198.
- 11J. S. Bednash, V. E. Kagan, J. A. Englert, D. Farkas, Y. Y. Tyurina, V. A. Tyurin, S. N. Samovich, L. Farkas, A. Elhance, F. Johns, H. Lee, L. Cheng, A. Majumdar, D. Jones, O. R. Mejia, M. Ruane-Foster, J. D. Londino, R. K. Mallampalli, R. T. Robinson, Transl. Res. 2022, 240, 1–16.
- 12P. Li, M. Jiang, K. Li, H. Li, Y. Zhou, X. Xiao, Y. Xu, S. Krishfield, P. E. Lipsky, G. C. Tsokos, X. Zhang, Nat. Immunol. 2021, 22, 1107–1117.
- 13H. Liu, F. Forouhar, T. Seibt, R. Saneto, K. Wigby, J. Friedman, X. Xia, M. S. Shchepinov, S. K. Ramesh, M. Conrad, B. R. Stockwell, Nat. Chem. Biol. 2022, 18, 91–100.
- 14
- 14aO. Weinreb, S. Mandel, M. B. H. Youdim, T. Amit, Free Radical Biol. Med. 2013, 62, 52–64;
- 14bH. Zheng, M. B. Youdim, L. M. Weiner, M. Fridkin, Biochem. Pharmacol. 2005, 70, 1642–1652.
- 15Y. Gu, Y. Li, J. Wang, L. Zhang, J. Zhang, Y. Wang, Eur. J. Med. Chem. 2023, 247, 115015.
- 16H. Feng, B. R. Stockwell, PLoS Biol. 2018, 16, e2006203.
- 17
- 17aX. Chen, R. Kang, G. Kroemer, D. Tang, Nat. Rev. Clin. Oncol. 2021, 18, 280–296;
- 17bZ. Wu, M. Zhong, Y. Liu, Y. Xiong, Z. Gao, J. Ma, G. Zhuang, X. Hong, Biotechnol. Appl. Biochem. 2022, 69, 190–197.
- 18T. Luo, Q. Zheng, L. Shao, T. Ma, L. Mao, M. Wang, Angew. Chem. Int. Ed. 2022, 61, e202206277; Angew. Chem. 2022, 134, e202206277.
- 19S. Liu, X. Zhao, S. Shui, B. Wang, Y. Cui, S. Dong, T. Yuwen, G. Liu, J. Med. Chem. 2022, 65, 12176–12187.
- 20K. A. Nguyen, L. Conilh, P. Falson, C. Dumontet, A. Boumendjel, Eur. J. Med. Chem. 2022, 244, 114863.
- 21
- 21aC. Li, X. Wu, C. Zheng, S. Xu, Y. Liu, J. Qin, X. Fan, Y. Ye, W. Fei, J. Mater. Chem. B 2022, 10, 7671–7693;
- 21bZ. Shen, J. Song, B. C. Yung, Z. Zhou, A. Wu, X. Chen, Adv. Mater. 2018, 30, 1704007;
- 21cJ. Shi, P. W. Kantoff, R. Wooster, O. C. Farokhzad, Nat. Rev. Cancer 2017, 17, 20–37.
- 22
- 22aG. Lei, Y. Zhang, P. Koppula, X. Liu, J. Zhang, S. H. Lin, J. A. Ajani, Q. Xiao, Z. Liao, H. Wang, B. Gan, Cell Res. 2020, 30, 146–162;
- 22bL. F. Ye, K. R. Chaudhary, F. Zandkarimi, A. D. Harken, C. J. Kinslow, P. S. Upadhyayula, A. Dovas, D. M. Higgins, H. Tan, Y. Zhang, M. Buonanno, T. J. C. Wang, T. K. Hei, J. N. Bruce, P. D. Canoll, S. K. Cheng, B. R. Stockwell, ACS Chem. Biol. 2020, 15, 469–484.
- 23J. Guo, B. Xu, Q. Han, H. Zhou, Y. Xia, C. Gong, X. Dai, Z. Li, G. Wu, Cancer Res. Treat. 2018, 50, 445–460.
- 24S. Xu, O. Chaudhary, P. Rodríguez-Morales, X. Sun, D. Chen, R. Zappasodi, Z. Xu, A. F. M. Pinto, A. Williams, I. Schulze, Y. Farsakoglu, S. K. Varanasi, J. S. Low, W. Tang, H. Wang, B. McDonald, V. Tripple, M. Downes, R. M. Evans, N. A. Abumrad, T. Merghoub, J. D. Wolchok, M. N. Shokhirev, P. C. Ho, J. L. Witztum, B. Emu, G. Cui, S. M. Kaech, Immunity 2021, 54, 1561–1577.e7.
- 25
- 25aB. Niu, K. Liao, Y. Zhou, T. Wen, G. Quan, X. Pan, C. Wu, Biomaterials 2021, 277, 121110;
- 25bH. Lin, S. Li, J. Wang, C. Chu, Y. Zhang, X. Pang, P. Lv, X. Wang, Q. Zhao, J. Chen, H. Chen, W. Liu, X. Chen, G. Liu, Nanoscale Horiz. 2019, 4, 190–195;
- 25cL. Zhou, C. Dong, L. Ding, W. Feng, L. Yu, X. Cui, Y. Chen, Nano Today 2021, 39, 101212;
- 25dQ. Jiang, K. Wang, X. Zhang, B. Ouyang, H. Liu, Z. Pang, W. Yang, Small 2020, 16, 2001704;
- 25eF. Zeng, L. Tang, Q. Zhang, C. Shi, Z. Huang, S. Nijiati, X. Chen, Z. Zhou, Angew. Chem. Int. Ed. 2022, 61, e202112925; Angew. Chem. 2022, 134, e202112925.
- 26
- 26aW. Wang, M. Green, J. E. Choi, M. Gijón, P. D. Kennedy, J. K. Johnson, P. Liao, X. Lang, I. Kryczek, A. Sell, H. Xia, J. Zhou, G. Li, J. Li, W. Li, S. Wei, L. Vatan, H. Zhang, W. Szeliga, W. Gu, R. Liu, T. S. Lawrence, C. Lamb, Y. Tanno, M. Cieslik, E. Stone, G. Georgiou, T. A. Chan, A. Chinnaiyan, W. Zou, Nature 2019, 569, 270–274;
- 26bM. Matsushita, S. Freigang, C. Schneider, M. Conrad, G. W. Bornkamm, M. Kopf, J. Exp. Med. 2015, 212, 555–568.
- 27
- 27aX. Chen, P. B. Comish, D. Tang, R. Kang, Front. Cell Dev. Biol. 2021, 9, 637162;
- 27bJ. Li, R. Kang, D. Tang, Methods Cell Biol. 2021, 165, 163–176;
- 27cH. Zheng, J. Jiang, S. Xu, W. Liu, Q. Xie, X. Cai, J. Zhang, S. Liu, R. Li, Nanoscale 2021, 13, 2266–2285.
- 28
- 28aD. Li, Y. Li, Signal Transduction Targeted Ther. 2020, 5, 108;
- 28bJ. Zheng, M. Conrad, Cell Metab. 2020, 32, 920–937;
- 28cD. Liang, A. M. Minikes, X. Jiang, Mol. Cell 2022, 82, 2215–2227;
- 28dH. Lee, F. Zandkarimi, Y. Zhang, J. K. Meena, J. Kim, L. Zhuang, S. Tyagi, L. Ma, T. F. Westbrook, G. R. Steinberg, D. Nakada, B. R. Stockwell, B. Gan, Nat. Cell Biol. 2020, 22, 225–234.
- 29R. L. Gonciarz, E. A. Collisson, A. R. Renslo, Trends Pharmacol. Sci. 2021, 42, 7–18.
- 30M. Gao, P. Monian, Q. Pan, W. Zhang, J. Xiang, X. Jiang, Cell Res. 2016, 26, 1021–1032.
- 31B. Hassannia, P. Vandenabeele, T. Vanden Berghe, Cancer Cell 2019, 35, 830–849.
- 32
- 32aW. S. Yang, B. R. Stockwell, Chem. Biol. 2008, 15, 234–245;
- 32bN. Geng, B. J. Shi, S. L. Li, Z. Y. Zhong, Y. C. Li, W. L. Xua, H. Zhou, J. H. Cai, Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 3826–3836.
- 33
- 33aS. W. Alvarez, V. O. Sviderskiy, E. M. Terzi, T. Papagiannakopoulos, A. L. Moreira, S. Adams, D. M. Sabatini, K. Birsoy, R. Possemato, Nature 2017, 551, 639–643;
- 33bJ. Du, T. Wang, Y. Li, Y. Zhou, X. Wang, X. Yu, X. Ren, Y. An, Y. Wu, W. Sun, W. Fan, Q. Zhu, Y. Wang, X. Tong, Free Radical Biol. Med. 2019, 131, 356–369;
- 33cH. Yuan, X. Li, X. Zhang, R. Kang, D. Tang, Biochem. Biophys. Res. Commun. 2016, 478, 838–844;
- 33dE. H. Kim, D. Shin, J. Lee, A. R. Jung, J.-L. Roh, Cancer Lett. 2018, 432, 180–190.
- 34
- 34aW. Hou, Y. Xie, X. Song, X. Sun, M. T. Lotze, H. J. Zeh 3rd, R. Kang, D. Tang, Autophagy 2016, 12, 1425–1428;
- 34bC. W. Brown, J. J. Amante, P. Chhoy, A. L. Elaimy, H. Liu, L. J. Zhu, C. E. Baer, S. J. Dixon, A. M. Mercurio, Dev. Cell 2019, 51, 575–586.e4.
- 35A. V. Menon, J. Liu, H. P. Tsai, L. Zeng, S. Yang, A. Asnani, J. Kim, Blood 2022, 139, 936–941.
- 36W. S. Yang, K. J. Kim, M. M. Gaschler, M. Patel, M. S. Shchepinov, B. R. Stockwell, Proc. Natl. Acad. Sci. USA 2016, 113, E4966–E4975.
- 37
- 37aP. Liao, W. Wang, W. Wang, I. Kryczek, X. Li, Y. Bian, A. Sell, S. Wei, S. Grove, J. K. Johnson, P. D. Kennedy, M. Gijón, Y. M. Shah, W. Zou, Cancer Cell 2022, 40, 365–378.e6;
- 37bB. Gan, Signal Transduction Targeted Ther. 2022, 7, 128;
- 37cH. L. Zhang, B. X. Hu, Z. L. Li, T. Du, J. L. Shan, Z. P. Ye, X. D. Peng, X. Li, Y. Huang, X. Y. Zhu, Y. H. Chen, G. K. Feng, D. Yang, R. Deng, X. F. Zhu, Nat. Cell Biol. 2022, 24, 88–98.
- 38D. Tang, G. Kroemer, Signal Transduction Targeted Ther. 2020, 5, 273.
- 39
- 39aM. K. Foret, R. Lincoln, S. Do Carmo, A. C. Cuello, G. Cosa, Chem. Rev. 2020, 120, 12757–12787;
- 39bM. Conrad, D. A. Pratt, Nat. Chem. Biol. 2019, 15, 1137–1147.
- 40
- 40aH. Bayır, T. S. Anthonymuthu, Y. Y. Tyurina, S. J. Patel, A. A. Amoscato, A. M. Lamade, Q. Yang, G. K. Vladimirov, C. C. Philpott, V. E. Kagan, Cell Chem. Biol. 2020, 27, 387–408;
- 40bY. Zou, S. L. Schreiber, Cell Chem. Biol. 2020, 27, 463–471.
- 41Y. Yao, Z. Chen, H. Zhang, C. Chen, M. Zeng, J. Yunis, Y. Wei, Y. Wan, N. Wang, M. Zhou, C. Qiu, Q. Zeng, H. S. Ong, H. Wang, F. V. Makota, Y. Yang, Z. Yang, N. Wang, J. Deng, C. Shen, Y. Xia, L. Yuan, Z. Lian, Y. Deng, C. Guo, A. Huang, P. Zhou, H. Shi, W. Zhang, H. Yi, D. Li, M. Xia, J. Fu, N. Wu, J. B. de Haan, N. Shen, W. Zhang, Z. Liu, D. Yu, Nat. Immunol. 2021, 22, 1127–1139.
- 42S. Bannai, J. Biol. Chem. 1986, 261, 2256–2263.
- 43M. Hayano, W. S. Yang, C. K. Corn, N. C. Pagano, B. R. Stockwell, Cell Death Differ. 2016, 23, 270–278.
- 44
- 44aS. Doll, F. P. Freitas, R. Shah, M. Aldrovandi, M. C. da Silva, I. Ingold, A. Goya Grocin, T. N. Xavier da Silva, E. Panzilius, C. H. Scheel, A. Mourão, K. Buday, M. Sato, J. Wanninger, T. Vignane, V. Mohana, M. Rehberg, A. Flatley, A. Schepers, A. Kurz, D. White, M. Sauer, M. Sattler, E. W. Tate, W. Schmitz, A. Schulze, V. O'Donnell, B. Proneth, G. M. Popowicz, D. A. Pratt, J. P. F. Angeli, M. Conrad, Nature 2019, 575, 693–698;
- 44bK. Bersuker, J. M. Hendricks, Z. Li, L. Magtanong, B. Ford, P. H. Tang, M. A. Roberts, B. Tong, T. J. Maimone, R. Zoncu, M. C. Bassik, D. K. Nomura, S. J. Dixon, J. A. Olzmann, Nature 2019, 575, 688–692;
- 44cC. Mao, X. Liu, Y. Zhang, G. Lei, Y. Yan, H. Lee, P. Koppula, S. Wu, L. Zhuang, B. Fang, M. V. Poyurovsky, K. Olszewski, B. Gan, Nature 2021, 593, 586–590;
- 44dV. A. N. Kraft, C. T. Bezjian, S. Pfeiffer, L. Ringelstetter, C. Müller, F. Zandkarimi, J. Merl-Pham, X. Bao, N. Anastasov, J. Kössl, S. Brandner, J. D. Daniels, P. Schmitt-Kopplin, S. M. Hauck, B. R. Stockwell, K. Hadian, J. A. Schick, ACS Cent. Sci. 2020, 6, 41–53;
- 44eE. Dai, L. Meng, R. Kang, X. Wang, D. Tang, Biochem. Biophys. Res. Commun. 2020, 522, 415–421.
- 45B. R. Stockwell, Cell 2022, 185, 2401–2421.
- 46Z. Wang, Y. Ding, X. Wang, S. Lu, C. Wang, C. He, L. Wang, M. Piao, G. Chi, Y. Luo, P. Ge, Cancer Lett. 2018, 428, 21–33.
- 47S. Wu, Y. Yan, H. Hou, Z. Huang, D. Li, X. Zhang, Y. Xiao, Anal. Chem. 2022, 94, 11238–11247.
- 48J. Yin, Q. Xu, X. Mo, L. Dai, M. Ren, S. Wang, F. Kong, Dyes Pigm. 2022, 200, 110184.
- 49Y. Xie, W. Hou, X. Song, Y. Yu, J. Huang, X. Sun, R. Kang, D. Tang, Cell Death Differ. 2016, 23, 369–379.
- 50C. Huang, Y. Sun, Y. Zhao, J. Li, L. Qu, R. Yang, Z. Li, ACS Appl. Bio Mater. 2022, 5, 2703–2711.
- 51X. Qian, Z. Xu, Chem. Soc. Rev. 2015, 44, 4487–4493.
- 52J. J. Vaquero, P. Kinahan, Annu. Rev. Biomed. Eng. 2015, 17, 385–414.
- 53
- 53aW. Breuer, S. Epsztejn, Z. I. Cabantchik, J. Biol. Chem. 1995, 270, 24209–24215;
- 53bF. Petrat, H. de Groot, U. Rauen, Arch. Biochem. Biophys. 2000, 376, 74–81.
- 54A. T. Aron, A. G. Reeves, C. J. Chang, Curr. Opin. Chem. Biol. 2018, 43, 113–118.
- 55Y. Lu, G. Ruan, W. Du, J. Li, N. Yang, Q. Wu, L. Lu, C. Zhang, L. Li, Dyes Pigm. 2021, 190, 109337.
- 56T. Hirayama, H. Tsuboi, M. Niwa, A. Miki, S. Kadota, Y. Ikeshita, K. Okuda, H. Nagasawa, Chem. Sci. 2017, 8, 4858–4866.
- 57W. Xing, H. Xu, H. Ma, S. A. A. Abedi, S. Wang, X. Zhang, X. Liu, H. Xu, W. Wang, K. Lou, Chem. Commun. (Camb.) 2022, 58, 2979–2982.
- 58
- 58aY. Tang, Y. Dong, X. Wang, S. Kamaraj, J. Wood, J. Vennerstrom, J. Org. Chem. 2005, 70, 5103–5110;
- 58bX. Wang, D. J. Creek, C. E. Schiaffo, Y. Dong, J. Chollet, C. Scheurer, S. Wittlin, S. A. Charman, P. H. Dussault, J. K. Wood, J. L. Vennerstrom, Bioorg. Med. Chem. Lett. 2009, 19, 4542–4545.
- 59B. Spangler, C. W. Morgan, S. D. Fontaine, M. N. Vander Wal, C. J. Chang, J. A. Wells, A. R. Renslo, Nat. Chem. Biol. 2016, 12, 680–685.
- 60A. T. Aron, M. O. Loehr, J. Bogena, C. J. Chang, J. Am. Chem. Soc. 2016, 138, 14338–14346.
- 61A. T. Aron, M. C. Heffern, Z. R. Lonergan, M. N. Vander Wal, B. R. Blank, B. Spangler, Y. Zhang, H. M. Park, A. Stahl, A. R. Renslo, E. P. Skaar, C. J. Chang, Proc. Natl. Acad. Sci. USA 2017, 114, 12669–12674.
- 62C. Shao, Y. Liu, Z. Chen, Y. Qin, X. Wang, X. Wang, C. Yan, H. L. Zhu, J. Zhao, Y. Qian, Cell Chem. Biol. 2022, 29, 43–56.e12.
- 63R. K. Muir, N. Zhao, J. Wei, Y. H. Wang, A. Moroz, Y. Huang, Y. C. Chen, R. Sriram, J. Kurhanewicz, D. Ruggero, A. R. Renslo, M. J. Evans, ACS Cent. Sci. 2019, 5, 727–736.
- 64N. Zhao, Y. Huang, Y. H. Wang, R. K. Muir, Y. C. Chen, J. Wei, N. Hooshdaran, P. Viswanath, Y. Seo, D. Ruggero, A. R. Renslo, M. J. Evans, J. Nucl. Med. 2021, 62, 949–955.
- 65
- 65aI. J. Schultz, C. Chen, B. H. Paw, I. Hamza, J. Biol. Chem. 2010, 285, 26753–26759;
- 65bT. Shimizu, A. Lengalova, V. Martínek, M. Martínková, Chem. Soc. Rev. 2019, 48, 5624–5657.
- 66S. Xu, H. W. Liu, L. Chen, J. Yuan, Y. Liu, L. Teng, S. Y. Huan, L. Yuan, X. B. Zhang, W. Tan, J. Am. Chem. Soc. 2020, 142, 2129–2133.
- 67K. Kawai, T. Hirayama, H. Imai, T. Murakami, M. Inden, I. Hozumi, H. Nagasawa, J. Am. Chem. Soc. 2022, 144, 3793–3803.
- 68L. A. Sklar, B. S. Hudson, R. D. Simoni, Proc. Natl. Acad. Sci. USA 1975, 72, 1649–1653.
- 69G. P. Drummen, L. C. van Liebergen, J. A. Op den Kamp, J. A. Post, Free Radical Biol. Med. 2002, 33, 473–490.
- 70K. Yamanaka, Y. Saito, J. Sakiyama, Y. Ohuchi, F. Oseto, N. Noguchi, RSC Adv. 2012, 2, 7894–7900.
- 71
- 71aA. A. Kapralov, Q. Yang, H. H. Dar, Y. Y. Tyurina, T. S. Anthonymuthu, R. Kim, C. M. St Croix, K. Mikulska-Ruminska, B. Liu, I. H. Shrivastava, V. A. Tyurin, H. C. Ting, Y. L. Wu, Y. Gao, G. V. Shurin, M. A. Artyukhova, L. A. Ponomareva, P. S. Timashev, R. M. Domingues, D. A. Stoyanovsky, J. S. Greenberger, R. K. Mallampalli, I. Bahar, D. I. Gabrilovich, H. Bayır, V. E. Kagan, Nat. Chem. Biol. 2020, 16, 278–290;
- 71bV. E. Kagan, G. Mao, F. Qu, J. P. Angeli, S. Doll, C. S. Croix, H. H. Dar, B. Liu, V. A. Tyurin, V. B. Ritov, A. A. Kapralov, A. A. Amoscato, J. Jiang, T. Anthonymuthu, D. Mohammadyani, Q. Yang, B. Proneth, J. Klein-Seetharaman, S. Watkins, I. Bahar, J. Greenberger, R. K. Mallampalli, B. R. Stockwell, Y. Y. Tyurina, M. Conrad, H. Bayır, Nat. Chem. Biol. 2017, 13, 81–90.
- 72J. C. Vickerman, Analyst 2011, 136, 2199–2217.
- 73L. J. Sparvero, H. Tian, A. A. Amoscato, W. Y. Sun, T. S. Anthonymuthu, Y. Y. Tyurina, O. Kapralov, S. Javadov, R. R. He, S. C. Watkins, N. Winograd, V. E. Kagan, H. Bayır, Angew. Chem. Int. Ed. 2021, 60, 11784–11788; Angew. Chem. 2021, 133, 11890–11894.
- 74Y. Matsuoka, Y. Izumi, M. Takahashi, T. Bamba, K. I. Yamada, Anal. Chem. 2020, 92, 6993–7002.
- 75N. Allocati, M. Masulli, C. Di Ilio, L. Federici, Oncogenesis 2018, 7, 8.
- 76A. T. M. Van Kessel, R. Karimi, G. Cosa, Chem. Sci. 2022, 13, 9727–9738.
- 77
- 77aS. Doll, M. Conrad, IUBMB Life 2017, 69, 423–434;
- 77bJ. P. Friedmann Angeli, S. Miyamoto, A. Schulze, Chem. Res. Toxicol. 2019, 32, 362–369.
- 78Y. Chen, Y. Liu, T. Lan, W. Qin, Y. Zhu, K. Qin, J. Gao, H. Wang, X. Hou, N. Chen, J. P. Friedmann Angeli, M. Conrad, C. Wang, J. Am. Chem. Soc. 2018, 140, 4712–4720.
- 79
- 79aG. Waeg, G. Dimsity, H. Esterbauer, Free Radical Res. 1996, 25, 149–159;
- 79bS. Toyokuni, N. Miyake, H. Hiai, M. Hagiwara, S. Kawakishi, T. Osawa, K. Uchida, FEBS Lett. 1995, 359, 189–191.
- 80H. Zheng, L. Jiang, T. Tsuduki, M. Conrad, S. Toyokuni, Redox. Biol. 2021, 48, 102175.
- 81S. Kobayashi, Y. Harada, T. Homma, C. Yokoyama, J. Fujii, J. Immunol. Methods 2021, 489, 112912.
- 82B. Feng, K. Wang, Z. Wang, H. Niu, G. Wang, Y. Chen, H. Zhang, Front. Chem. 2022, 10, 909670.
- 83X. Bao, X. Cao, Y. Yuan, B. Zhou, C. Huo, Sens. Actuators B 2021, 344, 130210.
- 84M. Ren, D. Dong, Q. Xu, J. Yin, S. Wang, F. Kong, Talanta 2021, 234, 122684.
- 85H. C. Zhang, D. H. Tian, Y. L. Zheng, F. Dai, B. Zhou, Spectrochim. Acta Part A 2021, 248, 119264.
- 86Z. Li, Y. Li, Y. Yang, Z. Gong, H. Zhu, Y. Qian, Anal. Chim. Acta 2020, 1125, 66–75.
- 87
- 87aS. J. Dixon, D. N. Patel, M. Welsch, R. Skouta, E. D. Lee, M. Hayano, A. G. Thomas, C. E. Gleason, N. P. Tatonetti, B. S. Slusher, B. R. Stockwell, eLife 2014, 3, e02523;
- 87bJ. Cao, A. Poddar, L. Magtanong, J. Lumb, T. Mileur, M. Reid, C. Dovey, J. Wang, E. Stone, S. Cole, J. Carette, S. Dixon, Cell Rep. 2019, 26, 1544–1556.e8.
- 88R. Hider, M. V. Aviles, Y. L. Chen, G. O. Latunde-Dada, Int. J. Mol. Sci. 2021, 22, 1278.
- 89X. Jiang, J. Chen, A. Bajić, C. Zhang, X. Song, S. L. Carroll, Z. L. Cai, M. Tang, M. Xue, N. Cheng, C. P. Schaaf, F. Li, K. R. MacKenzie, A. C. M. Ferreon, F. Xia, M. C. Wang, M. Maletić-Savatić, J. Wang, Nat. Commun. 2017, 8, 16087.
- 90
- 90aH. Feng, K. Schorpp, J. Jin, C. E. Yozwiak, B. G. Hoffstrom, A. M. Decker, P. Rajbhandari, M. E. Stokes, H. G. Bender, J. M. Csuka, P. S. Upadhyayula, P. Canoll, K. Uchida, R. K. Soni, K. Hadian, B. R. Stockwell, Cell Rep. 2020, 30, 3411–3423.e7;
- 90bM. Gao, P. Monian, N. Quadri, R. Ramasamy, X. Jiang, Mol. Cell 2015, 59, 298–308.
- 91Y. Shibata, H. Yasui, K. Higashikawa, Y. Kuge, Biochem. Biophys. Rep. 2021, 26, 100957.
- 92
- 92aT. Hirschhorn, B. R. Stockwell, Free Radical Biol. Med. 2019, 133, 130–143;
- 92bB. R. Stockwell, J. P. Friedmann Angeli, H. Bayir, A. I. Bush, M. Conrad, S. J. Dixon, S. Fulda, S. Gascón, S. K. Hatzios, V. E. Kagan, K. Noel, X. Jiang, A. Linkermann, M. E. Murphy, M. Overholtzer, A. Oyagi, G. C. Pagnussat, J. Park, Q. Ran, C. S. Rosenfeld, K. Salnikow, D. Tang, F. M. Torti, S. V. Torti, S. Toyokuni, K. A. Woerpel, D. D. Zhang, Cell 2017, 171, 273–285.
- 93J. Jin, K. Schorpp, D. Samaga, K. Unger, K. Hadian, B. R. Stockwell, ACS Chem. Biol. 2022, 17, 654–660.
- 94Y. C. Chen, J. A. Oses-Prieto, L. E. Pope, A. L. Burlingame, S. J. Dixon, A. R. Renslo, J. Am. Chem. Soc. 2020, 142, 19085–19093.
- 95C. Liang, X. Zhang, M. Yang, X. Dong, Adv. Mater. 2019, 31, 1904197.
- 96
- 96aZ. Shaghaghi, S. Motieian, M. Alvandi, A. Yazdi, B. Asadzadeh, S. Farzipour, S. Abbasi, Mini-Rev. Med. Chem. 2022, 22, 2271–2286;
- 96bY. Jin, Y. Zhuang, M. Liu, J. Che, X. Dong, Drug Discovery Today 2021, 26, 916–930.
- 97M. S. Blois, Nature 1958, 181, 1199–1200.
- 98R. Shah, L. A. Farmer, O. Zilka, A. T. M. Van Kessel, D. A. Pratt, Cell Chem. Biol. 2019, 26, 1594–1607.e7.
- 99
- 99aX. Yao, W. Li, D. Fang, C. Xiao, X. Wu, M. Li, Z. Luo, Adv. Sci. 2021, 8, 2100997;
- 99bU. E. Martinez-Outschoorn, M. Peiris-Pagés, R. G. Pestell, F. Sotgia, M. P. Lisanti, Nat. Rev. Clin. Oncol. 2017, 14, 11–31;
- 99cA. J. Wolpaw, C. V. Dang, Trends Cell Biol. 2018, 28, 201–212.
- 100
- 100aF. Yao, Y. Deng, Y. Zhao, Y. Mei, Y. Zhang, X. Liu, C. Martinez, X. Su, R. R. Rosato, H. Teng, Q. Hang, S. Yap, D. Chen, Y. Wang, M. M. Chen, M. Zhang, H. Liang, D. Xie, X. Chen, H. Zhu, J. C. Chang, M. J. You, Y. Sun, B. Gan, L. Ma, Nat. Commun. 2021, 12, 7333;
- 100bD. M. Kremer, B. S. Nelson, L. Lin, E. L. Yarosz, C. J. Halbrook, S. A. Kerk, P. Sajjakulnukit, A. Myers, G. Thurston, S. W. Hou, E. S. Carpenter, A. C. Andren, Z. C. Nwosu, N. Cusmano, S. Wisner, N. E. Mbah, M. Shan, N. K. Das, B. Magnuson, A. C. Little, M. R. Savani, J. Ramos, T. Gao, S. A. Sastra, C. F. Palermo, M. A. Badgley, L. Zhang, J. M. Asara, S. K. McBrayer, M. P. di Magliano, H. C. Crawford, Y. M. Shah, K. P. Olive, C. A. Lyssiotis, Nat. Commun. 2021, 12, 4860.
- 101
- 101aF. Wang, E. T. Graham, N. Naowarojna, Z. Shi, Y. Wang, G. Xie, L. Zhou, W. Salmon, J. M. Jia, X. Wang, Y. Huang, S. L. Schreiber, Y. Zou, Cell Chem. Biol. 2022, 29, 157–170.e6;
- 101bF. Wang, N. Naowarojna, Y. Zou, STAR Protoc. 2022, 3, 101189.
- 102Y. Zhao, Y. Li, S. Kuermanbayi, Y. Liu, J. Zhang, Z. Ye, H. Guo, K. Qu, F. Xu, F. Li, Anal. Chem. 2023, 95, 1940–1948.
- 103
- 103aJ. P. Friedmann Angeli, D. V. Krysko, M. Conrad, Nat. Rev. Cancer 2019, 19, 405–414;
- 103bR. Kim, A. Hashimoto, N. Markosyan, V. A. Tyurin, Y. Y. Tyurina, G. Kar, S. Fu, M. Sehgal, L. Garcia-Gerique, A. Kossenkov, B. A. Gebregziabher, J. W. Tobias, K. Hicks, R. A. Halpin, N. Cvetesic, H. Deng, L. Donthireddy, A. Greenberg, B. Nam, R. H. Vonderheide, Y. Nefedova, V. E. Kagan, D. I. Gabrilovich, Nature 2022, 612, 338–346;
- 103cB. Wiernicki, S. Maschalidi, J. Pinney, S. Adjemian, T. Vanden Berghe, K. S. Ravichandran, P. Vandenabeele, Nat. Commun. 2022, 13, 3676.
- 104
- 104aR. Yue, C. Zhang, L. Xu, Y. Wang, G. Guan, L. Lei, X. Zhang, G. Song, Chem 2022, 8, 1956–1981;
- 104bG. Guan, C. Zhang, H. Liu, Y. Wang, Z. Dong, C. Lu, B. Nan, R. Yue, X. Yin, X. B. Zhang, G. Song, Angew. Chem. Int. Ed. 2022, 61, e202117229; Angew. Chem. 2022, 134, e202117229.
- 105X. Song, Y. Xie, R. Kang, W. Hou, X. Sun, M. W. Epperly, J. S. Greenberger, D. Tang, Biochem. Biophys. Res. Commun. 2016, 480, 443–449.