YajL is the closest prokaryotic homologue of Parkinson's disease-associated DJ-1, a protein of undefined function involved in the oxidative stress response. We reported recently that YajL and DJ-1 protect cells against oxidative stress-induced protein aggregation by acting as covalent chaperones for the thiol proteome, including the NuoG subunit of NADH dehydrogenase 1, and that NADH dehydrogenase 1 activity is negligible in the mutant. We report here that this mutant compensates for low NADH dehydrogenase activity by utilizing NADH-independent alternative dehydrogenases, including pyruvate oxidase PoxB and -amino acid dehydrogenase DadA, and mixed acid aerobic fermentations characterized by acetate, lactate, succinate and ethanol excretion. The mutant has a low adenylate energy charge favouring glycolytic flux, and a high NADH/NAD ratio favouring fermentations over pyruvate dehydrogenase and the Krebs cycle. DNA array analysis showed upregulation of genes involved in glycolytic and pentose phosphate pathways and alternative respiratory pathways. Moreover, the mutant preferentially catabolized pyruvate-forming amino acids over Krebs cycle-related amino acids, and thus the mutant utilizes pyruvate-centred respiro-fermentative metabolism to compensate for the NADH dehydrogenase 1 defect and constitutes an interesting model for studying eukaryotic respiratory complex I deficiencies, especially those associated with Alzheimer's and Parkinson's diseases.


Article metrics loading...

Loading full text...

Full text loading...



  1. Abdallah J., Caldas T., Kthiri F., Kern R., Richarme G. (2007). YhbO protects cells against multiple stressesJ Bacteriol 18991409144 [View Article][PubMed]. [Google Scholar]
  2. Andersen K.B., von Meyenburg K. (1977). Charges of nicotinamide adenine nucleotides and adenylate energy charge as regulatory parameters of the metabolism in Escherichia coliJ Biol Chem 25241514156[PubMed]. [Google Scholar]
  3. Andres-Mateos E., Perier C., Zhang L., Blanchard-Fillion B., Greco T.M., Thomas B., Ko H.S., Sasaki M., Ischiropoulos H., other authors. (2007). DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidaseProc Natl Acad Sci U S A 1041480714812 [View Article][PubMed]. [Google Scholar]
  4. Auriol C., Bestel-Corre G., Claude J.B., Soucaille P., Meynial-Salles I. (2011). Stress-induced evolution of Escherichia coli points to original concepts in respiratory cofactor selectivityProc Natl Acad Sci U S A 10812781283 [View Article][PubMed]. [Google Scholar]
  5. Baba T., Ara T., Hasegawa M., Takai Y., Okumura Y., Baba M., Datsenko K.A., Tomita M., Wanner B.L., Mori H. (2006). Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collectionMol Syst Biol 20008 [View Article][PubMed]. [Google Scholar]
  6. Baev M.V., Baev D., Radek A.J., Campbell J.W. (2006). Growth of Escherichia coli MG1655 on LB medium: monitoring utilization of amino acids, peptides, and nucleotides with transcriptional microarraysAppl Microbiol Biotechnol 71317322 [View Article][PubMed]. [Google Scholar]
  7. Berríos-Rivera S.J., Sánchez A.M., Bennett G.N., San K.Y. (2004). Effect of different levels of NADH availability on metabolite distribution in Escherichia coli fermentation in minimal and complex mediaAppl Microbiol Biotechnol 65426432 [View Article][PubMed]. [Google Scholar]
  8. Bindoff L.A., Birch-Machin M., Cartlidge N.E., Parker W.D. Jr, Turnbull D.M. (1989). Mitochondrial function in Parkinson's diseaseLancet 33449 [View Article][PubMed]. [Google Scholar]
  9. Brumaghim J.L., Li Y., Henle E., Linn S. (2003). Effects of hydrogen peroxide upon nicotinamide nucleotide metabolism in Escherichia coli: changes in enzyme levels and nicotinamide nucleotide pools and studies of the oxidation of NAD(P)H by Fe(III)J Biol Chem 2784249542504 [View Article][PubMed]. [Google Scholar]
  10. Calhoun M.W., Gennis R.B. (1993). Demonstration of separate genetic loci encoding distinct membrane-bound respiratory NADH dehydrogenases in Escherichia coliJ Bacteriol 17530133019[PubMed]. [Google Scholar]
  11. Canet-Avilés R.M., Wilson M.A., Miller D.W., Ahmad R., McLendon C., Bandyopadhyay S., Baptista M.J., Ringe D., Petsko G.A., Cookson M.R. (2004). The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localizationProc Natl Acad Sci U S A 10191039108 [View Article][PubMed]. [Google Scholar]
  12. Clements C.M., McNally R.S., Conti B.J., Mak T.W., Ting J.P. (2006). DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2Proc Natl Acad Sci U S A 1031509115096 [View Article][PubMed]. [Google Scholar]
  13. Collier J., Bohn C., Bouloc P. (2004). SsrA tagging of Escherichia coli SecM at its translation arrest sequenceJ Biol Chem 2795419354201 [View Article][PubMed]. [Google Scholar]
  14. Cookson M.R. (2005). The biochemistry of Parkinson's diseaseAnnu Rev Biochem 742952 [View Article][PubMed]. [Google Scholar]
  15. Danielson S.R., Andersen J.K. (2008). Oxidative and nitrative protein modifications in Parkinson's diseaseFree Radic Biol Med 4417871794 [View Article][PubMed]. [Google Scholar]
  16. de Graef M.R., Alexeeva S., Snoep J.L., Teixeira de Mattos M.J. (1999). The steady-state internal redox state (NADH/NAD) reflects the external redox state and is correlated with catabolic adaptation in Escherichia coliJ Bacteriol 18123512357[PubMed]. [Google Scholar]
  17. Eiteman M.A., Altman E. (2006). Overcoming acetate in Escherichia coli recombinant protein fermentationsTrends Biotechnol 24530536 [View Article][PubMed]. [Google Scholar]
  18. Gautier V., Le H.T., Malki A., Messaoudi N., Caldas T., Kthiri F., Landoulsi A., Richarme G. (2012). YajL, the prokaryotic homolog of the Parkinsonism-associated protein DJ-1, protects cells against protein sulfenylationJ Mol Biol 421662670 [View Article][PubMed]. [Google Scholar]
  19. Guzman J.N., Sanchez-Padilla J., Wokosin D., Kondapalli J., Ilijic E., Schumacker P.T., Surmeier D.J. (2010). Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1Nature 468696700 [View Article][PubMed]. [Google Scholar]
  20. Holm A.K., Blank L.M., Oldiges M., Schmid A., Solem C., Jensen P.R., Vemuri G.N. (2010). Metabolic and transcriptional response to cofactor perturbations in Escherichia coliJ Biol Chem 2851749817506 [View Article][PubMed]. [Google Scholar]
  21. Husain M., Bourret T.J., McCollister B.D., Jones-Carson J., Laughlin J., Vázquez-Torres A. (2008). Nitric oxide evokes an adaptive response to oxidative stress by arresting respirationJ Biol Chem 28376827689 [View Article][PubMed]. [Google Scholar]
  22. Irrcher I., Aleyasin H., Seifert E.L., Hewitt S.J., Chhabra S., Phillips M., Lutz A.K., Rousseaux M.W.,, Bevilacqua L. & other authors (2010). Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamicsHum Mol Genet 1937343746 [View Article][PubMed]. [Google Scholar]
  23. Junn E., Taniguchi H., Jeong B.S., Zhao X., Ichijo H., Mouradian M.M. (2005). Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell deathProc Natl Acad Sci U S A 10296919696 [View Article][PubMed]. [Google Scholar]
  24. Koebmann B.J., Westerhoff H.V., Snoep J.L., Nilsson D., Jensen P.R. (2002). The glycolytic flux in Escherichia coli is controlled by the demand for ATPJ Bacteriol 18439093916 [View Article][PubMed]. [Google Scholar]
  25. Kthiri F., Gautier V., Le H.T., Prère M.F., Fayet O., Malki A., Landoulsi A., Richarme G. (2010a). Translational defects in a mutant deficient in YajL, the bacterial homolog of the Parkinsonism-associated protein DJ-1J Bacteriol 19263026306 [View Article][PubMed]. [Google Scholar]
  26. Kthiri F., Le H.T., Gautier V., Caldas T., Malki A., Landoulsi A., Bohn C., Bouloc P., Richarme G. (2010b). Protein aggregation in a mutant deficient in YajL, the bacterial homolog of the parkinsonism-associated protein DJ-1J Biol Chem 2851032810336 [View Article][PubMed]. [Google Scholar]
  27. Le H.T., Gautier V., Kthiri F., Malki A., Messaoudi N., Mihoub M., Landoulsi A., An Y.J., Cha S.S., Richarme G. (2012). YajL, prokaryotic homolog of Parkinsonism-associated protein DJ-1, functions as a covalent chaperone for thiol proteomeJ Biol Chem 28758615870 [View Article][PubMed]. [Google Scholar]
  28. Lee S.J., Kim S.J., Kim I.K., Ko J., Jeong C.S., Kim G.H., Park C., Kang S.O., Suh P.G., other authors. (2003). Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domainJ Biol Chem 2784455244559 [View Article][PubMed]. [Google Scholar]
  29. Lee K.J., Jeong C.S., An Y.J., Lee H.J., Park S.J., Seok Y.J., Kim P., Lee J.H., Lee K.H., Cha S.S. (2011). FrsA functions as a cofactor-independent decarboxylase to control metabolic fluxNat Chem Biol 7434436 [View Article][PubMed]. [Google Scholar]
  30. Lin S.J., Ford E., Haigis M., Liszt G., Guarente L. (2004). Caloric restriction extends yeast life span by lowering the level of NADHGenes Dev 181216 [View Article][PubMed]. [Google Scholar]
  31. Malki A., Caldas T., Abdallah J., Kern R., Eckey V., Kim S.J., Cha S.S., Mori H., Richarme G. (2005). Peptidase activity of the Escherichia coli Hsp31 chaperoneJ Biol Chem 2801442014426 [View Article][PubMed]. [Google Scholar]
  32. Messaoudi N., Gautier V., Kthiri F., Lelandais G., Mihoub M., Joseleau-Petit D., Caldas T., Bohn C., Tolosa L., other authors. (2013). Global stress response in a prokaryotic model of DJ-1-associated ParkinsonismJ Bacteriol 19511671178 [View Article][PubMed]. [Google Scholar]
  33. Noda S., Takezawa Y., Mizutani T., Asakura T., Nishiumi E., Onoe K., Wada M., Tomita F., Matsushita K., Yokota A. (2006). Alterations of cellular physiology in Escherichia coli in response to oxidative phosphorylation impaired by defective F1-ATPaseJ Bacteriol 18868696876 [View Article][PubMed]. [Google Scholar]
  34. Prüss B.M., Nelms J.M., Park C., Wolfe A.J. (1994). Mutations in NADH:ubiquinone oxidoreductase of Escherichia coli affect growth on mixed amino acidsJ Bacteriol 17621432150[PubMed]. [Google Scholar]
  35. Quigley P.M., Korotkov K., Baneyx F., Hol W.G. (2003). The 1.6-A crystal structure of the class of chaperones represented by Escherichia coli Hsp31 reveals a putative catalytic triadProc Natl Acad Sci U S A 10031373142 [View Article][PubMed]. [Google Scholar]
  36. Richarme G. (1987). Binding protein-dependent transports in 2-oxo acids dehydrogenase mutants of Escherichia coliBiochim Biophys Acta 893373377 [View Article][PubMed]. [Google Scholar]
  37. Sastry M.S., Korotkov K., Brodsky Y., Baneyx F. (2002). Hsp31, the Escherichia coli yedU gene product, is a molecular chaperone whose activity is inhibited by ATP at high temperaturesJ Biol Chem 2774602646034 [View Article][PubMed]. [Google Scholar]
  38. Schapira A.H., Gegg M. (2011). Mitochondrial contribution to Parkinson's disease pathogenesisParkinsons Dis 2011159160[PubMed]. [Google Scholar]
  39. Schiff M., Bénit P., Jacobs H.T., Vockley J., Rustin P. (2012). Therapies in inborn errors of oxidative metabolismTrends Endocrinol Metab 23488495 [View Article][PubMed]. [Google Scholar]
  40. Shendelman S., Jonason A., Martinat C., Leete T., Abeliovich A. (2004). DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formationPLoS Biol 2e362 [View Article][PubMed]. [Google Scholar]
  41. Unden G. (1998). Transcriptional regulations and energetics of alternative respiratory pathways in facultatively anaerobic bacteriaBiochim Biophys Acta 1365220224 [View Article]. [Google Scholar]
  42. Unden G., Bongaerts J. (1997). Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptorsBiochim Biophys Acta 1320217234 [View Article][PubMed]. [Google Scholar]
  43. van der Brug M.P., Blackinton J., Chandran J., Hao L.Y., Lal A., Mazan-Mamczarz K., Martindale J., Xie C., Ahmad R., other authors. (2008). RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathwaysProc Natl Acad Sci U S A 1051024410249 [View Article][PubMed]. [Google Scholar]
  44. Wallace B.J., Young I.G. (1977). Role of quinones in electron transport to oxygen and nitrate in Escherichia coli. Studies with a ubiA- menA- double quinone mutantBiochim Biophys Acta 46184100 [View Article][PubMed]. [Google Scholar]
  45. Wilson M.A., Collins J.L., Hod Y., Ringe D., Petsko G.A. (2003). The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's diseaseProc Natl Acad Sci U S A 10092569261 [View Article][PubMed]. [Google Scholar]
  46. Wilson M.A., Ringe D., Petsko G.A. (2005). The atomic resolution crystal structure of the YajL (ThiJ) protein from Escherichia coli: a close prokaryotic homologue of the Parkinsonism-associated protein DJ-1J Mol Biol 353678691 [View Article][PubMed]. [Google Scholar]
  47. Yohannes E., Barnhart D.M., Slonczewski J.L. (2004). pH-dependent catabolic protein expression during anaerobic growth of Escherichia coli K-12J Bacteriol 186192199 [View Article][PubMed]. [Google Scholar]
  48. Zhou W., Zhu M., Wilson M.A., Petsko G.A., Fink A.L. (2006). The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synucleinJ Mol Biol 35610361048 [View Article][PubMed]. [Google Scholar]

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error