Zinc Fingers as Biologic Redox Switches?

Despite zinc ions being redox inert in biologic systems, zinc-finger structures act as redox-sensitive molecular switches controlling several crucial cellular processes. Oxidative or nitrosative stress, via modification of zinc finger cysteine thiols, leads to a release of Zn2+ from these structures, causing not only a loss of zinc-finger function but also an increase of cytoplasmic or nuclear free Zn2+ that may, in turn, stimulate and interfere with cellular signaling cascades. A signaling cascade stimulated by exposure of cells to zinc ions or to stressful stimuli that are reported to cause an intracellular release of zinc ions involves phosphoinositide 3'-kinases and the Ser/Thr protein kinase Akt, resulting in an inactivation of transcriptional regulators of the FoxO family. Possible modes of action of zinc ions to stimulate this signaling cascade and consequences of stimulation are discussed. Moreover, we present an overview on human diseases or disorders characterized by an intracellular Zn2+ dyshomeostasis. Antioxid. Redox Signal. 11, 1015-1027.