title: Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism.
abstract: 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 yajL mutant. We report here that this mutant compensates for low NADH dehydrogenase activity by utilizing NADH-independent alternative dehydrogenases, including pyruvate oxidase PoxB and d-amino acid dehydrogenase DadA, and mixed acid aerobic fermentations characterized by acetate, lactate, succinate and ethanol excretion. The yajL 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 yajL mutant preferentially catabolized pyruvate-forming amino acids over Krebs cycle-related amino acids, and thus the yajL 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.
authors.affiliation: 1​Stress Molecules, Institut Jacques Monod, Université Paris 7, 2 place Jussieu, 75005 Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaoudi
authors.affiliation: 1​Stress Molecules, Institut Jacques Monod, Université Paris 7, 2 place Jussieu, 75005 Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gautier
authors.affiliation: 2​Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251, CNRS, Bioprofiler Facility, 75205, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
authors.affiliation: 1​Stress Molecules, Institut Jacques Monod, Université Paris 7, 2 place Jussieu, 75005 Paris, France.
authors.forename: Mouhad
authors.initials: M
authors.lastname: Mihoub
authors.affiliation: 1​Stress Molecules, Institut Jacques Monod, Université Paris 7, 2 place Jussieu, 75005 Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Lelandais
authors.affiliation: 3​Laboratoire de Signalisation et Réseaux de Régulations Bactériens, UMR 8621, Institut de Génétique et Microbiologie, Orsay, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouloc
authors.affiliation: 4​Laboratoire de Biochimie et Biologie Moléculaire 03/UR/0902, Faculté des Sciences de Bizerte, Zarzouna 7021, Bizerte, Tunisia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Landoulsi
authors.affiliation: 1​Stress Molecules, Institut Jacques Monod, Université Paris 7, 2 place Jussieu, 75005 Paris, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Richarme
mesh_terms: D000332:Aerobiosis; D004926:Escherichia coli / Q000201:enzymology* / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005285:Fermentation; D020869:Gene Expression Profiling; D006801:Humans; D064688:Metabolic Flux Analysis; D046228:Microarray Analysis; D008954:Models, Biological; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000172:deficiency*; D020734:Parkinsonian Disorders / Q000473:pathology; D012269:Ribosomal Proteins / Q000172:deficiency*; D017422:Sequence Analysis, DNA
chemical_list: D029968:Escherichia coli Proteins; D012269:Ribosomal Proteins; C554198:YajL protein, E coli; D009245:NADH Dehydrogenase