The identification of nitric oxide (NO) as a biological signaling molecule in animals in the 1980s has had an extraordinary impact on scientific research. Nowadays, NO impinges on almost all areas of biology, including vascular biology, neuroscience, immunology, and cancer research. Interestingly, the use of NO is not confined to the animal kingdom and the ability of fungi, bacteria, and plants to produce NO has been known for some time. Interest in NO as an endogenous signaling molecule in plants, however, did not gain impetus until the discovery by Durner et al. (Proc. Natl. Acad Sci. USA 95, 1998) and Delledonne et al. (Nature 394, 1998) that NO is a critical player in plants resisting pathogen infection. Clearly, both studies motivated searches for NO biosynthesis and action in plants. This research has now borne fruit with the recent identification of plant nitric oxide synthases (NOS) and the demonstration that NO plays an important role in diverse plant signaling processes, ranging from abscisic acid-mediated stomatal closure to programmed cell death. Our review conveyed the excitement generated by NO research in plants. This manuscript is highly cited because it represents the first comprehensive comparison of NO synthesis and signaling in animal and plant cells.

The review provided a survey of NO signaling in mammals and a detailed picture of its signaling activities in plants. The discussion opened up avenues for future research. Remarkably, some of the questions we asked have already been answered much further than we first anticipated!

The past few years have seen dramatic changes in our understanding of the molecular principles of host resistance. A growing body of evidence indicates that some of the molecular mechanisms involved in innate immunity in mammals and insects are strikingly similar to the molecular mechanisms underlying plant disease-resistance responses. It has been proposed, therefore, that innate immunity might be an evolutionarily ancient system of host defense. In mammals, the generation of NO by inducible NOS (iNOS) is the hallmark of innate immune responses, and NO plays an important role in inflammation, host defense responses, and tissue repair. For example, expression of iNOS often correlates with enhanced antimicrobial activity, while inhibitors of iNOS often increase susceptibility to pathogens. Considering the parallels between animal and plant defense responses, we asked ourselves whether the most versatile and powerful effector of animal redox-regulated signaling and immune responses, NO, mediates plant defense responses against pathogens.

  Could you summarize the significance of your paper in layman’s terms?

The fundamental message is that plants use NO as a signaling molecule via pathways remarkably similar to those found in mammals. That is, increasing data support the assumption that cGMP, Ca²⁺, cADPR, and NO-derived active oxygen species might serve as messengers for NO signaling in plants as reported in animals. Moreover, combination of biochemical, genetic, and confocal microscopy approaches provide clear evidences that plants produce NO through NOS-like enzymes located in certain subcellular compartments including chloroplasts, peroxisomes, and the nucleus. The fact that NO production in plants occurs in certain subcellular compartments may be critical both for specificity of targeting and for propagation of signals. In the animal fields, "identifying NO targets" is a strategy that scientists have embraced in their research, greatly helping in understanding how NO modulates cellular responses at the molecular level. Plant scientists should be inspired by this statement and should push NO research in plants way beyond of our peers.

David Wendehenne
Associate Professor
UMR INRA/CNRS/Université de Bourgogne 
Plante-Microbe-Environnement
Dijon, France