Abstract
Disulfidptosis is a novel discovered form of programmed cell death (PCD) that diverges from apoptosis, necroptosis, ferroptosis, and cuproptosis, stemming from disulfide stress-induced cytoskeletal collapse. In cancer cells exhibiting heightened expression of the solute carrier family 7 member 11 (SLC7A11), excessive cystine importation and reduction will deplete nicotinamide adenine dinucleotide phosphate (NADPH) under glucose deprivation, followed by an increase in intracellular disulfide stress and aberrant disulfide bond formation within actin networks, ultimately culminating in cytoskeletal collapse and disulfidptosis. Disulfidptosis involves crucial physiological processes in eukaryotic cells, such as cystine and glucose uptake, NADPH metabolism, and actin dynamics. The Rac1-WRC pathway-mediated actin polymerization is also implicated in this cell death due to its contribution to disulfide bond formation. However, the precise mechanisms underlying disulfidptosis and its role in tumors are not well understood. This is probably due to the multifaceted functionalities of SLC7A11 within cells and the complexities of the downstream pathways driving disulfidptosis. This review describes the critical roles of SLC7A11 in cells and summarizes recent research advancements in the potential pathways of disulfidptosis. Moreover, the less-studied aspects of this newly discovered cell death process are highlighted to stimulate further investigations in this field.