Nitric oxide and hydrogen sulfide share regulatory functions in higher plant events

Nitric oxide (NO) and hydrogen sulfide (H2S) are two molecules that share signaling properties in plant and animal cells. NO and H2S originate two families of derived molecules designated reactive nitrogen and sulfur species (RNS and RSS, respectively). These molecules are responsible for certain protein regulatory processes through posttranslational modifications (PTMs), being the most remarkable S-nitrosation and persulfidation, which affect the thiol group of cysteine residues. NO and H2S can also exert regulatory functions due to their interaction through the iron present in proteins that contain heme groups or iron-sulfur clusters, as reported mainly in animal cells. However, the available information in plant cells is still very limited thus far. In higher plants, NO and H2S are involved in a myriad of physiological events from seed germination to fruit ripening, but also the mechanism of response to biotic and abiotic stress conditions. This viewpoint manuscript highlights the functional regulatory parallelism of these two molecules which also interact with the metabolism of reactive oxygen species (ROS) in plant cells. Brief Historical Perspective Nitric oxide (NO) and hydrogen sulfide (H2S) are two gaseous molecules that were initially considered dangerous because they were associated with some detrimental effects on animal and plant cells. However, this perspective underwent a drastic change of mind when it was found that these molecules were endogenously generated in animal cells (Kolluru et al., 2013). There was a gap of about 10 years between the initial research works that described the signaling functions of either NO or H2S in living organisms. Accordingly, key research on NO, published in 1987 (Palmer et al., 1987), and on H2S in 1996 (Abe and Kimura, 1996) in animal systems provided the first pieces of evidence showing that these molecules exerted diverse signaling roles in the cardiovascular and nervous systems, respectively. Years later, plant biologists also found that these molecules were also endogenously generated in plant cells where they are involved in almost all of the stages of plant development including seed germination, root development, plant growth, stomata movement, senescence, flowering and fruit ripening (Leshem et al., 1998; Lamattina et al., 2003; Simontacchi et al., 2004; Corpas et al., 2004; Corpas et al., 2006; Corpas et al., 2008; Zhou et al., 2018; Chen et al., 2019; González-Gordo et al., 2019; Mukherjee and Corpas, 2020; Zuccarelli et al., 2021). And both compounds were also linked to the mechanisms of response against adverse environmental conditions triggered by either abiotic or biotic agents (Corpas, 2019; Kharbech et al., 2020; Iqbal et al., 2021). Fig. 1 illustrates the key functions in which NO and H2S have been shown to participate in higher plants. Chemistry and Biochemistry of NO and H2S Although NO and H2S are very simple molecules, their (bio) chemistry is more complex than it could be thought (Stamler et al., 1992; McCleverty, 2004; Hughes, 2008; Kabil and Banerjee, 2010; Filipovic et al., 2018; González-Gordo et al., 2020). NO is a colourless gas that belongs to the free radical-type molecules because it has an unpaired electron in the π orbital of the nitrogen atom, what is usually indicated with a dot in the chemical formula (NO). Some of the NO and H2S physical and chemical properties are: (i) Solubility of NO is 1.9 mM in aqueous solutions at 1 atm pressure, whereas the solubility of H2S is 100 mM at the same pressure; (ii) Their in vivo lifetime is relatively short, *Address correspondence to: Francisco J. Corpas, javier.corpas@eez.csic. es Received: 29 April 2021; Accepted: 01 June 2021 BIOCELL ech T Press Science 2022 46(1): 1-5 Doi: 10.32604/biocell.2021. 017300 www.techscience. com/journal/biocell This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. less than 10 seconds for NO and between second to few minutes for H2S. Therefore, they can trigger regulatory functions in cellular loci far from their production sites; (iii) NO and H2S are lipophilic molecules and they can diffuse across cell membranes; and, (iv) Both molecules can react with thiol groups from peptides and proteins affecting the function of the target molecules. Likewise, NO and H2S can also interact with iron containing-proteins, where the metal is present as either heme group or as part of the iron-sulfur cluster. Thus, there are multiple examples in higher plants where either NO and H2S, or both, can modulate, through their interaction with the cysteine thiol groups, the functions of proteins such as cytochrome c oxidase, catalase, Fe-superoxide dismutase, ascorbate peroxidase, ferredoxin(Fd)-NADP reductase, glutaredoxin, Fd-dependent glutamine:2-oxyoglutarate aminotransferase (Fd-GOGAT) or phytoglobins, (Ramirez et al., 2011; Aroca et al., 2017; Bahmani et al., 2019; Palma et al., 2020; Niu et al., 2019; Corpas et al., 2021). These proteins are involved in essential plant processes including photosynthesis, respiration, antioxidant system, nitrogen and sulfur assimilation, which remarks the physiological relevance of these signaling molecules. However, in higher plants, the available information about the direct interaction of NO and H2S with the iron side of protein is still scarce. In addition to reactions that can originate the respective families of molecules derived from nitric oxide and hydrogen sulfide (RNS and RSS, respectively), NO and H2S can interfere with the biosynthesis of each other and also produce novel species through their chemical interaction, thereby expanding the network of interactions that can affect to macromolecules (Kolluru et al., 2013; Scuffi et al., 2014; Kolluru et al., 2015; Hancock and Whiteman, 2016; Iqbal et al., 2021). S-nitrosation and Persulfidation: Two Protein PTMs that Exert Redox Control of Thiol Groups The amino acid cysteine (Cys) can play relevant roles in proteins such as a structural function through disulfide bonds, but it could also have implications on redox reactions by means of its thiol group (–SH). Thus, depending on the conditions surrounding the thiol group in the protein, Cys can be found in its anionic form, designated as thiolate (RS), which is a stronger nucleophilic agent than its protonated form (Netto et al., 2007). Fig. 2A depicts the different oxidation states of sulfur which range from thiol (–2) to sulfonic acid (+4). Among these states, NO or H2S can interact with the thiolate form through either S-nitrosation or persufidation (Fig. 2B), also known previously as protein S-nitrosylation and S-sulfhydration, respectively (Aroca et al., 2018; Wolhuter et al., 2018; Corpas et al., 2019, Corpas et al., 2021). For that reason, Cys is considered as a redox switch in the protein metabolism because it is the main target of these two PTMs, and this could affect significantly the biological activity of the corresponding protein, either positively or negatively. Ascorbate Peroxidase (APX) in Plant Cells: A Case Study of