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Review
. 2011 Oct 6;2(10):e213.
doi: 10.1038/cddis.2011.96.

Hydrogen peroxide: a Jekyll and Hyde signalling molecule

D R Gough  1 , T G Cotter
Affiliations
Review

Hydrogen peroxide: a Jekyll and Hyde signalling molecule

D R Gough et al. Cell Death Dis. .

Abstract

Reactive oxygen species (ROS) are a group of molecules produced in the cell through metabolism of oxygen. Endogenous ROS such as hydrogen peroxide (H₂O₂) have long been recognised as destructive molecules. The well-established roles they have in the phagosome and genomic instability has led to the characterisation of these molecules as non-specific agents of destruction. Interestingly, there is a growing body of literature suggesting a less sinister role for this Jekyll and Hyde molecule. It is now evident that at lower physiological levels, H₂O₂ can act as a classical intracellular signalling molecule regulating kinase-driven pathways. The newly discovered biological functions attributed to ROS include proliferation, migration, anoikis, survival and autophagy. Furthermore, recent advances in detection and quantification of ROS-family members have revealed that the diverse functions of ROS can be determined by the subcellular source, location and duration of these molecules within the cell. In light of this confounding paradox, we will examine the factors and circumstances that determine whether H₂O₂ acts in a pro-survival or deleterious manner.

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Figures

Figure 1
Figure 1
Nox2 structure. Exposure to pathogenic organism triggers Nox2 complex assembly in the neutrophil by recruiting various subunits to the plasma membrane. The activated Nox complex then releases superoxide in micromolar concentrations into the phagosome, thus killing the pathogen
Figure 2
Figure 2
Subcellular localisation of Nox-generated H2O2. Multi-photon microscopy images of Nox-generated ROS in MV411 acute myeloid leukaemia cells (courtesy of Dr Lavinia Bhatt). The ROS-sensitive dye, Peroxy Orange-1 (PO1), stains red in the presence of ROS. The fluorescence observed shows a staining pattern consistent with the endoplasmic reticulum
Figure 3
Figure 3
Nox regulation of the PI3K/AKT pathway. Activation of Nox activity occurs upon growth factor stimulation. This happens through recruitment of various protein subunits or by induction of Nox isoform expression. Nox-derived H2O2 then regulates kinase-driven survival signalling, for example, the PI3K/AKT pathway, by three major mechanisms. The cysteine residues located at the active sites of specific phosphatases are susceptible to reversible oxidation. This oxidation results in the inhibition of these phosphatases that negatively regulate survival signalling, thus propagating a pro-survival effect. Nox-generated ROS can also stimulate many pro-survival kinases (Src) and transcription factors (NF-kB), resulting in enhanced survival signalling
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