Downloaded from www.microbiologyresearch.org by IP: 54.70.40.11 On: Tue, 06 Nov 2018 08:18:11 Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism Nadia Messaoudi, 1 3 Vale ´ rie Gautier, 1 3 Julien Dairou, 2 Mouhad Mihoub, 1 Gae ¨ lle Lelandais, 1 Philippe Bouloc, 3 Ahmed Landoulsi 4 and Gilbert Richarme 1 Correspondence Gilbert Richarme richarme@paris7.jussieu.fr 1 Stress Molecules, Institut Jacques Monod, Universite ´ Paris 7, 2 place Jussieu, 75005 Paris, France 2 Universite ´ Paris Diderot, Sorbonne Paris Cite ´ , Unite ´ de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251, CNRS, Bioprofiler Facility, 75205, Paris, France 3 Laboratoire de Signalisation et Re ´ seaux de Re ´ gulations Bacte ´ riens, UMR 8621, Institut de Ge ´ne ´ tique et Microbiologie, Orsay, France 4 Laboratoire de Biochimie et Biologie Mole ´ culaire 03/UR/0902, Faculte ´ des Sciences de Bizerte, Zarzouna 7021, Bizerte, Tunisia 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. Received 16 June 2015 Revised 7 September 2015 Accepted 11 September 2015 INTRODUCTION YajL belongs to the PfpI/Hsp31/DJ-1 superfamily which includes chaperones (Quigley et al., 2003; Sastry et al., 2002), peptidases (Malki et al., 2005) and the Parkinson’s disease-associated protein DJ-1 (Canet-Avile ´s et al., 2004; Cookson, 2005). The crystal structures of YajL and DJ-1 are strikingly similar (Wilson et al., 2003, 2005), and their backbone structures are essentially identical (0.9 A ˚ C a root-mean-square deviation), suggesting that they have similar functions. DJ-1 is involved in the cellular response to oxidative stress, and has been suggested to function as a weak protease (Lee et al., 2003), an oxidative stress-activated chaperone (Le et al., 2012; Shendelman et al., 2004; Zhou et al., 2006), an atypical peroxiredoxin-like peroxidase (Andres-Mateos et al., 2007; Canet-Avile ´s et al., 2004), a stabilizer of the antioxidant transcriptional regulator Nrf2 (Clements et al., 2006), an apoptosis inhibitor via interaction with Daxx (Junn et al., 2005), a transcriptional or translational regulator of gene expression (Cookson, 2005; van der 3These authors contributed equally to this work. Abbreviation: PEP, phosphoenolpyruvate. The Gene Expression Omnibus accession number for the microarray experiments reported in this paper is GSE42702. Microbiology (2015), 161, 2220–2231 DOI 10.1099/mic.0.000181 000181 G 2015 The Authors Printed in Great Britain 2220