Cysteine/cystine couple is a newly recognized node in the circuitry for biologic redox signaling and control

SPECIFIC AIMSReversible oxidation of sulfur-containing side chains of cysteine and methionine in proteins functions in signaling and control of gene expression, cell proliferation, and apoptosis. Glutathione (GSH) and thioredoxin (Trx) systems maintain signaling components in a reduced state and are counterbalanced in signaling by oxidative mechanisms, typically thought to directly depend upon reactive oxygen species (ROS). However, in cisternae of the endoplasmic reticulum, an oxidase is used to generate an intermediate disulfide to oxidize target protein thiols by a thiol/disulfide exchange mechanism. In principle, similar systems could function elsewhere in redox signaling. Cystine is a ubiquitous disulfide generated from cysteine by an oxidase on extracellular surfaces, and cysteine/cystine redox state in human plasma is considerably oxidized relative to GSH/GSSG. If cysteine/cystine redox were similarly oxidized in cells, this system could function in redox signaling and control with cystine being an...