Disulfidptosis: Disulfide Stress Mediates a Novel Cell Death Pathway via Actin Cytoskeletal Vulnerability
Dongpu Shao, Lei Shi, Honglei Ji
Abstract
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.
Topics & Concepts
Pentose phosphate pathwayNicotinamide adenine dinucleotide phosphateIntracellularCytosolChemistryCystineCell biologyCytoskeletonCysteineNicotinamide adenine dinucleotideActinBiochemistryNAD+ kinaseCellGlycolysisEnzymeBiologyOxidase testNeutrophil, Myeloperoxidase and Oxidative MechanismsBiomedical Research and PathophysiologyHeme Oxygenase-1 and Carbon Monoxide