Abstract
Endothelial nitric oxide synthase (eNOS) is protective against kidney injury, but the molecular mechanisms of this protection are poorly understood1,2. Nitric oxide-based cellular signalling 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 that includes S-nitrosylases and denitrosylases, which add and remove SNO from proteins, respectively3,4. In Saccharomyces cerevisiae, the classic metabolic intermediate co-enzyme A (CoA) serves as an endogenous source of SNOs through its conjugation with nitric oxide to form S-nitroso-CoA (SNO-CoA), and 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 system is highly expressed in renal proximal tubules, where it transduces the activity of eNOS in reprogramming intermediary metabolism, thereby protecting kidneys against acute kidney injury. Specifically, deletion of Akr1a1 in mice to reduce SCoR activity increased protein S-nitrosylation, protected against acute kidney injury and improved survival, whereas this protection was lost when Enos (also known as Nos3) was also deleted. 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, which is refractory to S-nitrosylation, negated SNO-CoA bioactivity. Our results identify a physiological function of the SNO-CoA–SCoR system in mammals, describe new regulation of renal metabolism and of PKM2 in differentiated tissues, and offer a novel perspective on kidney injury with therapeutic implications.
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Data availability
The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information. All datasets generated and/or analysed in the current study are available from the corresponding author upon reasonable request. Supplementary Fig. 1 contains scanned complete images of western blots. All experimental data from mice models are provided as Source Data.
Change history
15 May 2019
Change history: In Fig. 1j of this Letter, one data point was inadvertently omitted from the graph for the acute kidney injury (AKI), double knockout (−/−), S-nitrosothiol (SNO) condition at a nitrosylation level of 25.9 pmol mg−1 and the statistical significance given of P = 0.0221 was determined by Fisher’s test instead of P = 0.0032 determined by Tukey’s test (with normalization for test-day instrument baseline). Figure 1 and its Source Data have been corrected online.
References
Wang, W. et al. Endothelial nitric oxide synthase-deficient mice exhibit increased susceptibility to endotoxin-induced acute renal failure. Am. J. Physiol. Renal Physiol. 287, F1044–F1048 (2004).
Forbes, M. S., Thornhill, B. A., Park, M. H. & Chevalier, R. L. Lack of endothelial nitric-oxide synthase leads to progressive focal renal injury. Am. J. Pathol. 170, 87–99 (2007).
Seth, D. et al. A multiplex enzymatic machinery for cellular protein S-nitrosylation. Mol. Cell 69, 451–464 (2018).
Stomberski, C. T., Hess, D. T. & Stamler, J. S. Protein S-nitrosylation: determinants of specificity and enzymatic regulation of S-nitrosothiol-based signaling. Antioxid. Redox Signal. https://doi.org/10.1089/ars.2017.7403 (2018).
Anand, P. et al. Identification of S-nitroso-CoA reductases that regulate protein S-nitrosylation. Proc. Natl Acad. Sci. USA 111, 18572–18577 (2014).
Nagasu, H. et al. Endothelial dysfunction promotes the transition from compensatory renal hypertrophy to kidney injury after unilateral nephrectomy in mice. Am. J. Physiol. Renal Physiol. 302, F1402–F1408 (2012).
Gabbay, K. H. et al. Ascorbate synthesis pathway: dual role of ascorbate in bone homeostasis. J. Biol. Chem. 285, 19510–19520 (2010).
Jia, J. et al. Target-selective protein S-nitrosylation by sequence motif recognition. Cell 159, 623–634 (2014).
Lan, R. et al. Mitochondrial pathology and glycolytic shift during proximal tubule atrophy after ischemic AKI. J. Am. Soc. Nephrol. 27, 3356–3367 (2016).
Kang, H. M. et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat. Med. 21, 37–46 (2015).
Chang, G. G. & Tong, L. Structure and function of malic enzymes, a new class of oxidative decarboxylases. Biochemistry 42, 12721–12733 (2003).
Gray, L. R., Tompkins, S. C. & Taylor, E. B. Regulation of pyruvate metabolism and human disease. Cell. Mol. Life Sci. 71, 2577–2604 (2014).
Anastasiou, D. et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334, 1278–1283 (2011).
Qi, W. et al. Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction. Nat. Med. 23, 753–762 (2017).
Fan, J. et al. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510, 298–302 (2014).
Kim, J. et al. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney. Am. J. Physiol. Renal Physiol. 296, F622–F633 (2009).
Sharfuddin, A. A. & Molitoris, B. A. Pathophysiology of ischemic acute kidney injury. Nat. Rev. Nephrol. 7, 189–200 (2011).
Granger, D. N. & Kvietys, P. R. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol. 6, 524–551 (2015).
Zuk, A. & Bonventre, J. V. Acute kidney injury. Annu. Rev. Med. 67, 293–307 (2016).
Ratliff, B. B., Abdulmahdi, W., Pawar, R. & Wolin, M. S. Oxidant mechanisms in renal injury and disease. Antioxid. Redox Signal. 25, 119–146 (2016).
Benavides, G. A., Liang, Q., Dodson, M., Darley-Usmar, V. & Zhang, J. Inhibition of autophagy and glycolysis by nitric oxide during hypoxia-reoxygenation impairs cellular bioenergetics and promotes cell death in primary neurons. Free Radic. Biol. Med. 65, 1215–1228 (2013).
Almeida, A., Moncada, S. & Bolaños, J. P. Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat. Cell Biol. 6, 45–51 (2004).
Bolaños, J. P., Delgado-Esteban, M., Herrero-Mendez, A., Fernandez-Fernandez, S. & Almeida, A. Regulation of glycolysis and pentose-phosphate pathway by nitric oxide: impact on neuronal survival. Biochim. Biophys. Acta 1777, 789–793 (2008).
O’Connor, T., Ireland, L. S., Harrison, D. J. & Hayes, J. D. Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. Biochem. J. 343, 487–504 (1999).
Alzeer, S. & Ellis, E. M. The role of aldehyde reductase AKR1A1 in the metabolism of γ-hydroxybutyrate in 1321N1 human astrocytoma cells. Chem. Biol. Interact. 191, 303–307 (2011).
Barski, O. A., Tipparaju, S. M. & Bhatnagar, A. The aldo-keto reductase superfamily and its role in drug metabolism and detoxification. Drug Metab. Rev. 40, 553–624 (2008).
Doulias, P. T., Tenopoulou, M., Greene, J. L., Raju, K. & Ischiropoulos, H. Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation. Sci. Signal. 6, rs1 (2013).
Anastasiou, D. et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat. Chem. Biol. 8, 839–847 (2012).
Christofk, H. R. et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452, 230–233 (2008).
Ye, J. et al. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc. Natl Acad. Sci. USA 109, 6904–6909 (2012).
Israelsen, W. J. et al. PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells. Cell 155, 397–409 (2013).
Shao, X., Somlo, S. & Igarashi, P. Epithelial-specific Cre/lox recombination in the developing kidney and genitourinary tract. J. Am. Soc. Nephrol. 13, 1837–1846 (2002).
Tran, M. T. et al. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature 531, 528–532 (2016).
Forrester, M. T. et al. Proteomic analysis of S-nitrosylation and denitrosylation by resin-assisted capture. Nat. Biotechnol. 27, 557–559 (2009).
Zhou, H. L., Geng, C., Luo, G. & Lou, H. The p97–UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated HuR from mRNP. Genes Dev. 27, 1046–1058 (2013).
Stamler, J. S. et al. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc. Natl Acad. Sci. USA 89, 7674–7677 (1992).
Solez, K., Morel-Maroger, L. & Sraer, J. D. The morphology of “acute tubular necrosis” in man: analysis of 57 renal biopsies and a comparison with the glycerol model. Medicine (Baltimore) 58, 362–376 (1979).
Conger, J. D., Schultz, M. F., Miller, F. & Robinette, J. B. Responses to hemorrhagic arterial pressure reduction in different ischemic renal failure models. Kidney Int. 46, 318–323 (1994).
Fujioka, H., Tandler, B. & Hoppel, C. L. Mitochondrial division in rat cardiomyocytes: an electron microscope study. Anat. Rec. (Hoboken) 295, 1455–1461 (2012).
Hanaichi, T. et al. A stable lead by modification of Sato’s method. J. Electron Microsc. (Tokyo) 35, 304–306 (1986).
Hitosugi, T. et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci. Signal. 2, ra73 (2009).
Paynter, N. P. et al. Metabolic predictors of incident coronary heart disease in women. Circulation 137, 841–853 (2018).
Acknowledgements
We thank H. Fujioka for mitochondrial analyses, J. Mikulan and A. Kresak for histology and immunostaining, C. Geng for assistance with statistics, and J. Reynolds, D. Hess, R. Premont and D. Seth for discussions. This work is supported by National Institutes of Health grants DK119506, HL075443, HL128192 and HL126900.
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Nature thanks H. Christofk, C. Lowenstein and G. Remuzzi for their contribution to the peer review of this work.
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H.-L.Z., P.A. and J.S.S. designed the study. H.-L.Z. carried out most of the experiments and analysed the results. R.Z. performed AKI surgery. P.A. prepared samples for iTRAQ LC–MS/MS and metabolomics. C.T.S. prepared samples for the photolysis-chemiluminescence assay. A.H. and P.A. purified SCoR from bovine kidney. Z.Q. handled mice. L.W. performed quantitative iTRAQ LC–MS/MS. E.P.R. and S.M.P. contributed to project conception and carried out metabolomics analyses. S.A.K. contributed to project conception and performed histological stains. H.-L.Z. and J.S.S. wrote the manuscript with input from all authors.
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Extended data figures and tables
Extended Data Fig. 1 Identification of enzymes involved in the SNO-CoA–SCoR system.
a, b, Enzymatic mechanism by which the SNO-CoA–SCoR system regulates protein S-nitrosylation. a, Equilibrium between SNO-CoA and S-nitrosylated proteins. b, AKR1A1 (SCoR) mediates protein denitrosylation. c, AKR1A1 was purified to homogeneity using the indicated steps. AKR1A1 protein at each stage was calculated on the basis of activity in each eluate pool or original crude lysate. Image is representative of two independently performed experiments with similar results. d, e, Expression of iNOS, nNOS and eNOS in sham-treated versus injured kidneys of wild-type mice; injury induced by I/R. Images are representative of three independently performed experiments with similar results. For gel source data, see Supplementary Fig. 1. f, Expression of eNOS before and after AKI; normalized to GAPDH as in e (n = 8 mice per group). Results are presented as mean ± s.d. Two-tailed Student’s t-test was used to detect significance. g, Schema illustrating generation of Akr1a1−/− mice. h, PCR amplification of the Akr1a1 gene with genomic DNA isolated from the tails of Akr1a1+/+, heterozygous Akr1a1+/− and homozygous Akr1a1−/− mice. Image is representative of three independently performed experiments with similar results.
Extended Data Fig. 2 SCoR activity and role in protection.
a, b, Expression of AKR1A1 after I/R-induced AKI. Expression of AKR1A1 is normalized to GAPDH in b (n = 6 mice per group). c, NADPH-dependent SNO-CoA metabolizing activity measured in kidney extracts from sham-treated wild-type mice or wild-type mice subjected to I/R-induced AKI (n = 9 mice per group). d, Serum creatinine and BUN in sham-treated kidneys from Akr1a1+/+, Akr1a1−/−, Akr1a1−/−Enos−/− and Enos−/− mice (Akr1a1+/+: n = 41 mice; Akr1a1−/−: n = 35 mice; Akr1a1−/−Enos−/−: n = 10 mice; Enos−/−: n = 10 mice). Note lower scales (y axis) compared to Fig. 1e, f. e, Haematoxylin and eosin stain of sham-treated kidneys from Akr1a1+/+, Akr1a1−/− and Akr1a1−/−Enos−/− mice. Images are representative of two independently performed experiments with similar results. Scale bars, 50 μm. f, Pathological scores of tubular lysis, loss of brush border and sloughed debris (n = 5 mice per group). Results are presented as mean ± s.d. One-way ANOVA with Tukey post hoc test was used to detect significance. g, Mortality of Akr1a1+/+, Akr1a1−/−, Akr1a1−/−Enos−/− and Enos−/− mice 24 h after AKI (Akr1a1+/+: 35 mice; Akr1a1−/−: 36 mice; Akr1a1−/−Enos−/−: 12 mice; Enos−/−: 8 mice). Results are presented as mean ± s.d. One-way ANOVA with Tukey post hoc test was used to detect significance in d, f. Two-tailed Student’s t-test was used to detect significance in b, c.
Extended Data Fig. 3 Additional models of AKI.
a, Serum ascorbate in Akr1a1+/+ and Akr1a1−/− mice fed with chow containing 1% ascorbic acid for six weeks (n = 4 mice per group). b, c, Serum creatinine and BUN in injured kidneys from Akr1a1+/+ and Akr1a1−/− mice fed with chow containing 1% ascorbic acid for six weeks (n = 4 mice per group); injury by I/R. d, e, Serum creatinine and BUN in sham-treated or injured kidneys from female Akr1a1+/+ and female Akr1a1−/− mice (sham-treated Akr1a1+/+: n = 11 mice; sham-treated Akr1a1−/−: n = 12 mice; injured Akr1a1+/+: n = 25 mice; injured Akr1a1−/−: n = 31 mice). Injury by I/R. f, g, Serum creatinine and BUN in saline-treated or LPS-treated male Akr1a1+/+ and Akr1a1−/− mice (saline-treated Akr1a1+/+: n = 7 mice; saline-treated Akr1a1−/−: n = 5 mice; LPS-treated Akr1a1+/+: n = 11 mice; LPS-treated Akr1a1−/−: n = 11 mice). h, i, Serum creatinine and BUN in saline-treated or LPS-treated female Akr1a1+/+ and Akr1a1−/− mice (saline-treated Akr1a1+/+: n = 6 mice; saline-treated Akr1a1−/−: n = 3 mice; LPS-treated Akr1a1+/+: n = 12 mice; LPS-treated Akr1a1−/−: n = 15 mice). j, Endogenous S-nitrosylation of PKM2 in saline-treated or LPS-treated male Akr1a1+/+ and Akr1a1−/− mice. Data are representative of three mice per genotype. Without ascorbate (–Ascorbate) is control for SNO. k, Quantification of SNO-PKM2. SNO normalized to PKM2 (input) (n = 4 mice per group). l, Activity of endogenous pyruvate kinase in saline- or LPS-treated kidneys from Akr1a1+/+ and Akr1a1−/− mice (n = 3 mice per saline-treated group; n = 5 mice per LPS-treated group). Results are presented as mean ± s.d. One-way ANOVA with Tukey post hoc test was used to detect significance a, d–i, k, l. Two-tailed Student’s t-test was used to detect significance in b, c.
Extended Data Fig. 4 PK interactions, activity and expression.
a, Interaction between AKR1A1 and PKM2. Myc–PKM2 and V5–AKR1A1 were co-overexpressed in HEK-293 cells. Immunoprecipitation with anti-Myc rabbit antibody; immunoblotting with V5 antibody. Image is representative of two independently performed experiments with similar results. b, Activity of recombinant PKM2, PKM1 and PKLR proteins after SNO-CoA treatment (n = 3 independent experiments). Results are presented as mean ± s.d. One-way ANOVA with Tukey post hoc test was used to assess significance. c, Expression of PKM2, PKM1 and PKLR in the kidneys of Akr1a1+/+ and Akr1a1−/− mice after 24 h of I/R-induced AKI. Image is representative of two independently performed experiments with similar results. d, Quantification of expression of PKM2, PKM1 and PKLR in c (n = 6 mice per group). Result is presented as mean ± s.d. Two-tailed Student’s t-test was used to detect significance.
Extended Data Fig. 5 Characterization of SNO-PKM2.
a, Endogenous SNO level of PKM2 Cys-mutants in eNOS-overexpressing HEK-293 cells. Image is representative of two independently performed experiments with similar results. b, Mutation of C152 to alanine affects the SNO level of PKM2 in eNOS-overexpressing HEK-293 cells. Image is representative of two independently performed experiments with similar results. c, Quantification of expression of Myc–PKM2(WT), Myc–PKM2(C49A) and Myc–PKM2(C152A) in eNOS-overexpressing HEK-293 cells. Normalized to the expression of GAPDH (n = 5 independent experiments). d, Quantification of SNO-PKM2 in eNOS-overexpressing HEK-293 cells. SNO is normalized to PKM2 (input) (n = 5 independent experiments). e, Relative mRNA levels of Myc–PKM2(WT), Myc–PKM2(C49A) and Myc–PKM2(C152A) in eNOS-overexpressing HEK-293 cells (n = 3 independent experiments). Results presented as mean ± s.d. One-way ANOVA with Tukey post hoc test was used to detect significance.
Extended Data Fig. 6 Pkm gene, structure and expression.
a, Alternative splicing of Pkm gene. C423 and C424 are encoded by PKM2-specific exon 10. b, Ribbon structure of tetrameric PKM2 analysed by MacPyMOL. Four pairs of C423 and C424 in tetrameric PKM2 are highlighted in red. c, Expression of PKM1 and PKM2 in fifteen different tissues from uninjured mice. Image is representative of two independently performed experiments with similar results.
Extended Data Fig. 7 Role of PKM2 in AKR1A1-mediated protection.
a, Expression of endogenous and overexpressed PKM2 in HEK-293 cells. Image is representative of two independently performed experiments with similar results. b, Activity of Myc–PKM2(WT) and Myc–PKM2(C423/424A) after NO (DETANO; 500 μM) treatment in HEK-293 cells (n = 3 independent experiments). c, The total amount of GSH and GSSG in injured kidneys from Akr1a1+/+, Akr1a1−/− and Akr1a1−/−Enos−/− mice (n = 4 mice per group); injury induced by I/R. d, The amount of 6PG, a key PPP intermediate, in HEK-293 cells expressing Myc–PKM2(WT) and Myc–PKM2(C423/424A) after NO (DETANO; 500 μM) treatment (n = 4 independent experiments). e, Amount of serine in injured kidneys from Akr1a1+/+ and Akr1a1−/− mice (n = 10 mice per I/R-injured Akr1a1+/+ group; n = 11 mice per I/R-injured Akr1a1−/− group). f, Amount of serine in HEK-293 cells expressing Myc–PKM2(WT) and Myc–PKM2(C423/424A) after NO treatment (DETANO; 500 μM) (n = 4 independent experiments). g, Amount of GHB in serum of Akr1a1+/+ and Akr1a1−/− mice (n = 7 mice per group). No injury. Results are presented as mean ± s.d. One-way ANOVA with Tukey post hoc test was used to detect significance in b and f. Two-tailed Student’s t-test was used in e.
Extended Data Fig. 8 Mechanism of kidney injury.
a, Mitochondrial morphology in tubule cells after sham operation or injury induced by I/R from Akr1a1+/+ and Akr1a1−/− mice as assessed by electron microscopy. Red arrows, mitochondrial swelling. Scale bars, 1 μm. b, Quantification of swollen mitochondria versus total mitochondria in sham-treated or I/R-injured kidneys from Akr1a1+/+ and Akr1a1−/− mice. Results are presented as mean ± s.d. One-way ANOVA with Tukey post hoc was used to detect significance. c, The ratio of ADP to ATP in HEK-293 cells expressing Myc–PKM2(WT) or Myc–PKM2(C423/424A) after NO treatment (DETANO; 500 μM) (n = 4 independent experiments). d, Amounts of TCA cycle intermediates (aconitate, isocitrate, succinate, fumarate and malate) in sham-treated or injured kidneys from Akr1a1+/+ and Akr1a1−/− mice (n = 10 mice per sham-treated Akr1a1+/+ or I/R-injured Akr1a1+/+ group; n = 11 mice per sham-treated Akr1a1−/− or I/R-injured Akr1a1−/−group). Results are presented as mean ± s.d. There were no significant differences in c, d using one-way ANOVA with Tukey’s post hoc test.
Extended Data Fig. 9 Characterization of Pkm2−/− mice.
a, Schema illustrating generation of renal epithelial cell-specific Pkm2−/− mice. b, Survival curve following I/R-induced AKI (23 wild-type mice; 20 Pkm2−/− mice). Survival was analysed using Kaplan–Meier estimation. Gehan–Breslow–Wilcoxon test was used to detect significance. c, PEP in injured kidneys from wild-type and Pkm2−/− mice (n = 6 mice per group); injury induced by I/R. d, Pyruvate in injured kidneys from wild-type and Pkm2−/− mice (n = 6 mice per group). Results in c, d are presented as mean ± s.d. Two-tailed Student’s t-test was used to detect significance.
Extended Data Fig. 10 Expression of PKM1, PKM2 and PKLR after AKI.
a, Immunostaining showing expression of PKM2 in sham or injured kidneys of wild-type mice on the indicated days after surgery; injury induced by I/R. Images are representative of two independently performed experiments with similar results. b, Western blot showing expression of PKM2, PKM1 and PKLR in sham or injured kidneys of wild-type mice; injury induced by I/R. Images are representative of two independently performed experiments with similar results. c, Quantification of expression of PKM2, PKM1 and PKLR in b (n = 3 mice). Results are presented as mean ± s.d. One-way ANOVA with Tukey’s post hoc test was used to detect significance.
Supplementary information
Supplementary Figures
This file contains scanned complete images of western blots
Supplementary Tables
This file contains Supplementary Tables 1-3. Supplementary Table 1: SNO-proteins enriched ≥1.4 fold in injured Akr1a1-/- kidneys vs. Akr1a1+/+, detected by SNO-RAC-coupled quantitative iTRAQ MS. Supplementary Table 2: AKR1A1 interactome in mouse kidney by IP-MS. Supplementary Table 3: Shared targets identified in both the S-nitrosoproteome and AKR1A1 interactome
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Zhou, HL., Zhang, R., Anand, P. et al. Metabolic reprogramming by the S-nitroso-CoA reductase system protects against kidney injury. Nature 565, 96–100 (2019). https://doi.org/10.1038/s41586-018-0749-z
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DOI: https://doi.org/10.1038/s41586-018-0749-z
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