Abstract
Oxidative stress is an unavoidable peril that aerobic organisms have to confront. Thus, it is not surprising that intricate strategies are deployed in an effort to fend the dangers associated with living in an O2 environment. In the classical models of anti-oxidative defense mechanisms, a variety of stratagems including the reactive oxygen species (ROS) scavenging systems, the NADPH-generating enzymes and the DNA repair machineries are highlighted. However, it is becoming increasingly clear that metabolism may be intimately involved in anti-oxidative defence. Recent data show that metabolic reprogramming plays a pivotal role in the survival of organisms exposed to oxidative stress. Here, we describe how Pseudomonas fluorescens, the metabolically-versatile soil microbe, manipulates its metabolic networks in an effort to counter oxidative stress. An intricate link between metabolism and anti-oxidative defense is presented. P. fluorescens reconfigures its metabolic processes in an effort to satisfy its need for NADPH during oxidative insult. Seemingly, disparate metabolic modules appear to partner together to concomitantly fine-tune the levels of the anti-oxidant NADPH and the pro-oxidant NADH. Central to this shift in the metabolic production of the pyridine nucleotides is the increase in NAD kinase with the concomitant decrease in NADP phosphatase. The tricarboxylic acid cycle is tweaked in an effort to limit the formation of NADH. This metabolic redox-balancing act appears to afford a potent tool against oxidative challenge and may be a more widespread ROS-combating tactic than hitherto recognized.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adam-Vizi V, Chinopoulos C (2006) Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 27:639–645
Agledal L, Niere M, Ziegler M (2010) The phosphate makes a difference: cellular functions of NADP. Redox Rep 15:2–10
Ambrus A, Tretter L, Adam-Vizi V (2009) Inhibition of the alpha-ketoglutarate dehydrogenase-mediated reactive oxygen species generation by lipoic acid. J Neurochem 109(Suppl 1):222–229
Anderson S, Appanna VD, Huang J, Viswanatha T (1992) A novel role for calcite in calcium homeostasis. FEBS Lett 308:94–96
Aon MA, Cortassa S, O’Rourke B (2010) Redox-optimized ROS balance: a unifying hypothesis. Biochim Biophys Acta 1797:865–877
Bergamini CM, Gambetti S, Dondi A, Cervellati C (2004) Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des 10:1611–1626
Beriault R, Hamel R, Chenier D, Mailloux RJ, Joly H, Appanna VD (2007) The overexpression of NADPH-producing enzymes counters the oxidative stress evoked by gallium, an iron mimetic. Biometals 20:165–176
Boveris A, Sies H, Martino EE, Docampo R, Turrens JF, Stoppani AO (1980) Deficient metabolic utilization of hydrogen peroxide in Trypanosoma cruzi. Biochem J 188:643–648
Cabiscol E, Tamarit J, Ros J (2000) Oxidative stress in bacteria and protein damage by reactive oxygen species. Int Microbiol 3:3–8
Chai MF, Chen QJ, An R, Chen YM, Chen J, Wang XC (2005) NADK2, an Arabidopsis chloroplastic NAD kinase, plays a vital role in both chlorophyll synthesis and chloroplast protection. Plant Mol Biol 59:553–564
Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605
Chenier D, Beriault R, Mailloux R, Baquie M, Abramia G, Lemire J, Appanna V (2008) Involvement of fumarase C and NADH oxidase in metabolic adaptation of Pseudomonas fluorescens cells evoked by aluminum and gallium toxicity. Appl Environ Microbiol 74:3977–3984
Cohen G (1994) Enzymatic/nonenzymatic sources of oxyradicals and regulation of antioxidant defenses. Ann N Y Acad Sci 738:8–14
Cornelis P (2008) Unexpected interaction of a siderophore with aluminum and its receptor. J Bacteriol 190:6541–6543
Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95
Dunn SD, Chandler J (1998) Characterization of a b2delta complex from Escherichia coli ATP synthase. J Biol Chem 273:8646–8651
Fedotcheva NI, Sokolov AP, Kondrashova MN (2006) Nonezymatic formation of succinate in mitochondria under oxidative stress. Free Radic Biol Med 41:56–64
Forman HJ, Maiorino M, Ursini F (2010) Signaling functions of reactive oxygen species. Biochemistry 49:835–842
Gonzalez-Flecha B, Demple B (1995) Metabolic sources of hydrogen peroxide in aerobically growing Escherichia coli. J Biol Chem 270:13681–13687
Grose JH, Joss L, Velick SF, Roth JR (2006) Evidence that feedback inhibition of NAD kinase controls responses to oxidative stress. Proc Natl Acad Sci USA 103:7601–7606
Hamel R, Appanna VD (2003) Aluminum detoxification in Pseudomonas fluorescens is mediated by oxalate and phosphatidylethanolamine. Biochim Biophys Acta 1619:70–76
Hansford RG, Hogue BA, Mildaziene V (1997) Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. J Bioenerg Biomembr 29:89–95
Havir EA, McHale NA (1990) Purification and characterization of an isozyme of catalase with enhanced-peroxidatic activity from leaves of Nicotiana sylvestris. Arch Biochem Biophys 283:491–495
Hirst J, King MS, Pryde KR (2008) The production of reactive oxygen species by complex I. Biochem Soc Trans 36:976–980
Imlay JA (2008) Cellular defenses against superoxide and hydrogen peroxide. Annu Rev Biochem 77:755–776
Ingledew WJ, Poole RK (1984) The respiratory chains of Escherichia coli. Microbiol Rev 48:222–271
Iuchi S, Weiner L (1996) Cellular and molecular physiology of Escherichia coli in the adaptation to aerobic environments. J Biochem 120:1055–1063
Kawai S, Murata K (2008) Structure and function of NAD kinase and NADP phosphatase: key enzymes that regulate the intracellular balance of NAD(H) and NADP(H). Biosci Biotechnol Biochem 72:919–930
Kirkman HN, Rolfo M, Ferraris AM, Gaetani GF (1999) Mechanisms of protection of catalase by NADPH. Kinetics and stoichiometry. J Biol Chem 274:13908–13914
Kornberg A, Pricer WE Jr (1950) On the structure of triphosphopyridine nucleotide. J Biol Chem 186:557–567
Lee HC, Kim JS, Jang W, Kim SY (2009) Thymidine production by overexpressing NAD + kinase in an Escherichia coli recombinant strain. Biotechnol Lett 31:1929–1936
Lemire J, Mailloux R, Auger C, Whalen D, Appanna VD (2010a) Pseudomonas fluorescens orchestrates a fine metabolic-balancing act to counter aluminium toxicity. Environ Microbiol 12:1384–1390
Lemire J, Milandu Y, Auger C, Bignucolo A, Appanna VP, Appanna VD (2010b) Histidine is a source of the antioxidant, alpha-ketoglutarate, in Pseudomonas fluorescens challenged by oxidative stress. FEMS Microbiol Lett 309:170–177
Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J 3rd, Olefsky J, Guarente L, Montminy M (2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456:269–273
Maddipati KR, Marnett LJ (1987) Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase. J Biol Chem 262:17398–17403
Magni G, Amici A, Emanuelli M, Raffaelli N, Ruggieri S (1999) Enzymology of NAD + synthesis. Adv Enzymol Relat Areas Mol Biol 73:135–182 xi
Mailloux RJ, Harper ME (2010) Glucose regulates enzymatic sources of mitochondrial NADPH in skeletal muscle cells; a novel role for glucose-6-phosphate dehydrogenase. Faseb J 24:2495–2506
Mailloux RJ, Singh R, Appanna VD (2006) In-gel activity staining of oxidized nicotinamide adenine dinucleotide kinase by blue native polyacrylamide gel electrophoresis. Anal Biochem 359:210–215
Mailloux RJ, Beriault R, Lemire J, Singh R, Chenier DR, Hamel RD, Appanna VD (2007) The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. PLoS One 2:e690
Mailloux RJ, Lemire J, Kalyuzhnyi S, Appanna V (2008) A novel metabolic network leads to enhanced citrate biogenesis in Pseudomonas fluorescens exposed to aluminum toxicity. Extremophiles 12:451–459
McGuinness ET, Butler JR (1985) NAD + kinase—a review. Int J Biochem 17:1–11
Meyer JM (2000) Pyoverdines: pigments, siderophores and potential taxonomic markers of fluorescent Pseudomonas species. Arch Microbiol 174:135–142
Minard KI, McAlister-Henn L (2005) Sources of NADPH in yeast vary with carbon source. J Biol Chem 280:39890–39896
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13
O’Sullivan DJ, O’Gara F (1992) Traits of fluorescent Pseudomonas spp. involved in suppression of plant root pathogens. Microbiol Rev 56:662–676
Paulsen IT, Press CM, Ravel J, Kobayashi DY, Myers GS, Mavrodi DV, DeBoy RT, Seshadri R, Ren Q, Madupu R, Dodson RJ, Durkin AS, Brinkac LM, Daugherty SC, Sullivan SA, Rosovitz MJ, Gwinn ML, Zhou L, Schneider DJ, Cartinhour SW, Nelson WC, Weidman J, Watkins K, Tran K, Khouri H, Pierson EA, Pierson LS 3rd, Thomashow LS, Loper JE (2005) Complete genome sequence of the plant commensal Pseudomonas fluorescens Pf-5. Nat Biotechnol 23:873–878
Pollak N, Dolle C, Ziegler M (2007a) The power to reduce: pyridine nucleotides–small molecules with a multitude of functions. Biochem J 402:205–218
Pollak N, Niere M, Ziegler M (2007b) NAD kinase levels control the NADPH concentration in human cells. J Biol Chem 282:33562–33571
Singh R, Mailloux RJ, Puiseux-Dao S, Appanna VD (2007) Oxidative stress evokes a metabolic adaptation that favors increased NADPH synthesis and decreased NADH production in Pseudomonas fluorescens. J Bacteriol 189:6665–6675
Singh R, Lemire J, Mailloux RJ, Appanna VD (2008) A novel strategy involved in [corrected] anti-oxidative defense: the conversion of NADH into NADPH by a metabolic network. PLoS One 3:e2682
Singh R, Lemire J, Mailloux RJ, Chenier D, Hamel R, Appanna VD (2009) An ATP and oxalate generating variant tricarboxylic acid cycle counters aluminum toxicity in Pseudomonas fluorescens. PLoS One 4:e7344
Sung JY, Lee YN (2007) Isoforms of glucose 6-phosphate dehydrogenase in Deinococcus radiophilus. J Microbiol 45:318–325
Tretter L, Adam-Vizi V (2005) Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos Trans R Soc Lond B Biol Sci 360:2335–2345
Vattanaviboon P, Panmanee W, Mongkolsuk S (2003) Induction of peroxide and superoxide protective enzymes and physiological cross-protection against peroxide killing by a superoxide generator in Vibrio harveyi. FEMS Microbiol Lett 221:89–95
Winterbourn CC, French JK, Claridge RF (1978) Superoxide dismutase as an inhibitor of reactions of semiquinone radicals. FEBS Lett 94:269–272
Woo HA, Yim SH, Shin DH, Kang D, Yu DY, Rhee SG (2010) Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. Cell 140:517–528
Ying W (2008) NAD +/NADH and NADP +/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal 10:179–206
Acknowledgments
This work was supported by the Northern Ontario Heritage Fund, Ontario Center of Excellence, and Industry Canada. J. Lemire is a recipient of the Alexander Graham Bell doctoral fellowship.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mailloux, R.J., Lemire, J. & Appanna, V.D. Metabolic networks to combat oxidative stress in Pseudomonas fluorescens . Antonie van Leeuwenhoek 99, 433–442 (2011). https://doi.org/10.1007/s10482-010-9538-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10482-010-9538-x