Disulfidptosis: Disulfide Stress Mediates a Novel Cell Death Pathway via Actin Cytoskeletal Vulnerability

Schematic illustration of disulfidptosis.Cystine is transported to intracellular compartments by solute carrier family 7 member 11 (SLC7A11).Nicotinamide adenine dinucleotide phosphate (NADPH) is generated in the cytosol through the pentose phosphate pathway (PPP).In the presence of the reducing agent NADPH, one molecule of cystine is reduced to two molecules of cysteine, accompanied by oxidation of NADPH to NADP + .The F-actin cytoskeleton contracts due to aberrant disulfide bonding.Cells can survive if the reduced form of NADPH counteracts the accumulation of intracellular disulfides.Disulfidptosis is induced if the balance between cystine and NADPH/NADP + is disrupted.