Int J Biochem Cell Biol. 2026 Oct 29:107059. doi: 10.1016/j.biocel.2026.107059. Online ahead of print.
ABSTRACT
Regulated cell death (RCD) is intimately linked to the onset, progression, and therapeutic outcomes of diseases. Disulfidptosis represents a newly identified form of RCD that is mechanistically distinct from conventional modalities such as apoptosis, pyroptosis, ferroptosis, and cuproptosis. This novel mechanism is driven by solute carrier family 7 member 11 (SLC7A11)-mediated cystine uptake and concomitant reduced nicotinamide adenine dinucleotide phosphate (NADPH) depletion, which together provoke disulfide stress and collapse of the actin cytoskeleton and lamellipodia. Exploiting this vulnerability holds considerable therapeutic promise for cancers characterized by metabolically fragile and for oxidative stress-related disorders. In this review, we summarize the core mechanisms underlying disulfidptosis, with emphasis on SLC7A11-dependent cystine transport, NADPH homeostasis, disulfide stress, and cytoskeletal collapse. We further distinguish experimentally validated regulators from disulfidptosis-related gene (DRG) signatures derived from bioinformatic analyses, and outline three categories of therapeutic strategies. Beyond oncology, we discuss the emerging relevance of disulfidptosis across degenerative, cardiovascular, metabolic, and genetic diseases and conclude with an outlook on future research directions and unresolved challenges in disulfidptosis.
PMID:42956965 | DOI:10.1016/j.biocel.2026.107059