Signal Transduct Target Ther. 2026 Sep 8;11(1):379. doi: 10.1038/s41392-026-03001-y.
ABSTRACT
Cell death is essential for maintaining internal stability and metabolic balance in the human body and plays a key role in regulating physiological and pathological processes. Advances in understanding the link between pathological mechanisms and cell death have provided new insights into diagnosis and treatment. A novel, pivotal form of regulated cell death, termed disulfidptosis, has recently been identified. This is characterized by glucose deprivation, elevated expression of solute carrier family 7 member 11 (SLC7A11), accumulation of disulfides such as cystine, disulfide stress, and cell death. These distinctive characteristics indicate that disulfidptosis is mechanistically distinct from other known forms of cell death. Its unique induction mechanism implies its therapeutic potential and warrants further investigation. This cell death process is primarily triggered by intracellular NADPH exhaustion and subsequent actin cytoskeleton collapse, and it exhibits complex crosstalk with ferroptosis, cuproptosis, pyroptosis, necroptosis, apoptosis and autophagy. The core execution relies on the Rac-WRC-Arp2/3 pathway, with emerging involvement of ER stress and p38 MAPK signaling. In this review, we discuss the molecular mechanisms and current status and prospects of targeted therapy for disulfidptosis, as well as its role in cancer and other diseases, including but not limited to neurodegenerative, cardiovascular, autoimmune, and infectious conditions. We hope to provide a comprehensive and systematic framework, including mechanistic analysis, application strategies, clinical translation, and future research directions, to guide in-depth investigation.
PMID:42711333 | DOI:10.1038/s41392-026-03001-y