The metabolism of aerobic organisms continuously produces reactive oxygen species. Although potentially toxic, these compounds also function in signaling. One important feature of signaling compounds is their ability to move between different compartments, e.g. to cross membranes. Here we present evidence that aquaporins can channel hydrogen peroxide (H 2 O 2 ). Twenty-four aquaporins from plants and mammals were screened in five yeast strains differing in sensitivity toward oxidative stress. Expression of human AQP8 and plant Arabidopsis TIP1;1 and TIP1;2 in yeast decreased growth and survival in the presence of H 2 O 2 . Further evidence for aquaporin-mediated H 2 O 2 diffusion was obtained by a fluorescence assay with intact yeast cells using an intracellular reactive oxygen species-sensitive fluorescent dye. Application of silver ions (Ag ؉ ), which block aquaporin-mediated water diffusion in a fast kinetics swelling assay, also reversed both the aquaporindependent growth repression and the H 2 O 2 -induced fluorescence. Our results present the first molecular genetic evidence for the diffusion of H 2 O 2 through specific members of the aquaporin family.Hydrogen peroxide (H 2 O 2 ) 2 belongs to the group of reactive oxygen species (ROS). ROS are generated in a number of key metabolic processes in cells like the electron transport chain in the inner mitochondrial membrane (1) and, specific for plants, the chloroplast thylakoid membrane (2).Because ROS can potentially damage proteins, lipids, and nucleic acids, cells have a number of ROS-scavenging systems that are able to remove these molecules and to maintain a relatively low and constant ROS concentration (3). However, ROS are also intermediates in various signal transduction pathways and have been shown to initiate responses to various stresses and disorders (for recent reviews, see Refs. 4 and 5). Arabidopsis mutants lacking an NADPH oxidase were not able to respond adequately to potassium deficiency (6) and were impaired in stomatal closure (7), providing genetic evidence for a role of NADPH oxidase in signaling.ROS are interconvertible molecules including singlet oxygen, superoxide, hydroxyl radical, and H 2 O 2 . H 2 O 2 has a distinctive set of features compared with other ROS. (i) It is not charged, (ii) it is not a radical, (iii) it possesses an intermediate oxidation number, (iv) it is relatively stable under physiological conditions, and (v) catalase can disproportionate it into water and molecular oxygen without the expense of reduction equivalents.Although substantial progress has been made regarding the formation and scavenging of ROS, little is known about their transport from the site of origin to the place of action or detoxification. Recently three studies from mammalian systems have provided evidence that H 2 O 2 , in addition to the well studied role in intracellular signaling, is also used as an intercellular signal molecule (8 -10). This implies that a necessary step within these signal transduction pathways is the transport of H 2 O 2 ...

Hydrogen peroxide (H2O2) belongs to the reactive oxygen species (ROS), known as oxidants that can react with various cellular targets thereby causing cell damage or even cell death. On the other hand, recent work has demonstrated that H2O2 also functions as a signalling molecule controlling different essential processes in plants and mammals. Because of these opposing functions the cellular level of H2O2 is likely to be subjected to tight regulation via processes involved in production, distribution and removal. Substantial progress has been made exploring the formation and scavenging of H2O2, whereas little is known about how this signal molecule is transported from its site of origin to the place of action or detoxification. From work in yeast and bacteria it is clear that the diffusion of H2O2 across membranes is limited. We have now obtained direct evidence that selected aquaporin homologues from plants and mammals have the capacity to channel H2O2 across membranes. The main focus of this review is (i) to summarize the most recent evidence for a signalling role of H2O2 in various pathways in plants and mammals and (ii) to discuss the relevance of specific transport of H2O2.

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