Ethylene signaling plays important roles in multiple aspects of plant growth and development. Its functions in abiotic stress responses remain largely unknown. Here, we report that alteration of ethylene signaling affected plant salt-stress responses. A type II ethylene receptor homolog gene NTHK1 (Nicotiana tabacum histidine kinase 1) from tobacco (N. tabacum) conferred salt sensitivity in NTHK1-transgenic Arabidopsis (Arabidopsis thaliana) plants as judged from the phenotypic change, the relative electrolyte leakage, and the relative root growth under salt stress. Ethylene precursor 1-aminocyclopropane-1-carboxylic acid suppressed the salt-sensitive phenotype. Analysis of Arabidopsis ethylene receptor gain-of-function mutants further suggests that receptor function may lead to salt-sensitive responses. Mutation of EIN2, a central component in ethylene signaling, also results in salt sensitivity, suggesting that EIN2-mediated signaling is beneficial for plant salt tolerance. Overexpression of the NTHK1 gene or the receptor gain-of-function activated expression of salt-responsive genes AtERF4 and Cor6.6. In addition, the transgene NTHK1 mRNA was accumulated under salt stress, suggesting a posttranscriptional regulatory mechanism. These findings imply that ethylene signaling may be required for plant salt tolerance.

Endothelial nitric oxide (NO) synthase (eNOS) is protective against kidney injury, but the molecular mechanisms are poorly understood 1 , 2 . NO-based cellular signaling is generally mediated by protein S-nitrosylation, the oxidative modification of Cys residues to form S-nitrosothiols (SNOs). S-nitrosylation regulates proteins in all functional classes, and is controlled by enzymatic machinery including S-nitrosylases and denitrosylases that add and remove SNO from proteins, respectively 3 , 4 . We recently reported in Saccharomyces cerevisiae that the classic metabolic intermediate Co-enzymeA (CoA) serves as an endogenous source of SNOs through its conjugation with NO to form S-nitroso-CoA (SNO-CoA), and that S-nitrosylation of proteins by SNO-CoA is governed by its cognate denitrosylase, SNO-CoA reductase (SCoR) 5 . Mammals possess a functional homologue of yeast SCoR, an aldo-keto reductase family member (AKR1A1) 5 with an unknown physiological role. Here we report that the SNO-CoA/AKR1A1 (SCoR) system is highly expressed in renal proximal tubules where it transduces the activity of eNOS in reprogramming intermediary metabolism, thereby protecting kidneys from acute kidney injury (AKI). Specifically, AKR1A1 deletion in mice to reduce SCoR activity increased protein S-nitrosylation, protected against AKI and improved survival, whereas renoprotection was lost in Akr1a1 −/− / eNOS −/− mice. Metabolic profiling coupled with unbiased mass spectrometry-based SNO-protein identification revealed that protection by the SNO-CoA/SCoR system is mediated by inhibitory S-nitrosylation of pyruvate kinase M2 (PKM2) through a novel locus of regulation, thereby balancing fuel utilization (through glycolysis) with redox protection (through the pentose phosphate shunt). Targeted deletion of PKM2 from mouse proximal tubules recapitulated precisely the protective and mechanistic effects of S-nitrosylation in Akr1a1 −/− mice, whereas Cys-mutant PKM2 refractory to S-nitrosylation negated SNO-CoA bioactivity. Our discoveries provide a first physiological function of the SNO-CoA/SCoR system in mammals, reveal novel regulation of renal metabolism and of PKM2 in differentiated tissues in particular, and offer a new perspective on kidney injury with therapeutic implications.