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. 2024 Jun 17;29(9-10):1309–1329. doi: 10.1007/s10495-024-01989-8

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — The core molecular mechanisms of disulfidptosis. When the NADPH supply is limited under glucose deprivation conditions, high cystine uptake by cells with high SLC7A11 expression results in intracellular NADPH depletion, the excessive accumulation of cystine and other disulfide molecules, and abnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. Rac1-WRC-mediated branched actin polymerization and lamellipodia formation likely provide supporting conditions for disulfide bond formation in actin cytoskeleton proteins, thereby facilitating disulfidptosis. Abbreviations: SLC7A11, solute carrier family 7 member 11; SLC3A2, solute carrier family 3 member 2; GLUT1/4, glucose transporter 1/4; PPP, pentose phosphate pathway; NADPH, nicotinamide adenine dinucleotide phosphate; GSH, glutathione; GSSG, oxidized glutathione; GPX4, glutathione peroxidase 4; Arp2/3, actin-related protein 2/3 complex; RAC1, RAS-related C3 botulinum toxin substrate 1; WRC, WAVE regulatory complex; HSPC300, hematopoietic stem/progenitor cell protein 300; NCKAP1, NCK-associated protein 1; CYFIP1, cytoplasmic FMR1-interacting protein 1