Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4′-dipyridyl disulfide

• DOI: 10.1111/j.1567-1364.2006.00202.x
• Publication Date: 2007-01-24T13:15:00Z
• Authors: H. Reynaldo Lópe...; Michael Thorsen; Morten C. Kiellan...; Michel B. Toledano; Jakob R. Winther
• Keywords: Glutathione disulfide; Thiol; Glutaredoxin; GPX1; Glutathione reductase

Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma-glutamyl-cysteine synthetase) and, particularly, GLR1 (glutathione reductase) are required for survival on DPS. uniquely thiol-specific, and we found the cellular mechanisms detoxification differ substantially from of commonly used diamide. In contrast this oxidant, full antioxidant pools glutathione (GSH) thioredoxin resistance We DPS-sensitive mutants display increases form GSH (GSSG) during exposure roughly correlate with their more oxidizing redox potential cytosol degree sensitivity. seems induce specific stress, where an increase cytoplasmic/nuclear GSSG/GSH ratio results putative target(s) becoming sensitive