YajL, Prokaryotic Homolog of Parkinsonism-associated Protein DJ-1, Functions as a Covalent Chaperone for Thiol Proteome

Abstract

Background: A novel function for YajL, the prokaryotic homolog of the Parkinsonism-associated protein DJ-1. Results: YajL and DJ-1 form mixed disulfides with members of the thiol proteome. Conclusion: This covalent chaperone function supports their role in oxidative stress protection. Significance: There is an exciting encounter between the crucial cysteine 106 of these covalent chaperones and the oxidized cysteines of their substrates.

Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism

“…The WT strain and the yajL mutant oxidized NADH at relative rates of 100 and 29, respectively, and deamino-NADH at relative rates of 41 and 5.3, respectively (Fig. 1d); thus NADH dehydrogenase I was almost inactive in the mutant (13 % of the parental strain activity, as reported previously; Le et al, 2012) [we also reported previously that the YajL-overproducing plasmid efficiently rescued (up to 86 %) the NADH dehydrogenase defect of the yajL mutant; Le et al, 2012)], whereas NADH dehydrogenase 2 was 41 % active. The weak global NADH dehydrogenase activity of the yajL mutant may be responsible for the high NADH/NAD ratio, fermentative metabolism and induction of alternative respiratory pathways (see below).…”

“…Eukaryotic D-amino acid oxidases (which are restricted to D-amino acid detoxification) are of limited metabolic interest. Eukaryotic acyl-CoA dehydrogenases are involved in the first step of fatty acyl-CoA degradation and transfer hydrogens to quinones; however, the next oxidoreduction step of b-oxidation and acetyl-CoA oxidation in the Krebs cycle produce NADH, so they would be of little use to overcome NADH dehydrogenase defects (Abdallah et al, 2007;Bindoff et al, 1989;Calhoun & Gennis, 1993;Koebmann et al, 2002;Le et al, 2012;Schapira & Gegg, 2011). Proline oxidase catalyses the conversion of proline to D 1 -pyrroline-5-carboxylate and transfers hydrogens to quinones via FAD, whereas the reverse reaction, catalysed by D 1 -pyrroline-5-carboxylate reductase, uses NAD(P)H as a cofactor; consequently, both reactions produce a cycle of proline synthesis and degradation that can transfer redox potential between cellular compartments, and might contribute to bypassing NADH dehydrogenase 1 deficiency.…”

Identification of 2-oxohistidine Interacting Proteins Using E. coli Proteome Chips

“…YajL is an anti-oxidative-stress chaperone, which promotes disulfide formation to help maintain order in the thiol proteome (69). Interestingly, the human homolog of YajL, DJ-1, is also an antioxidative stress protein, and its mutations are known to cause familial Parkinsonism (70).…”

Protein Synthesis and the Stress Response

“…Also, several macromolecules that participate in translation have been found to be a target of oxidation in in vivo or in vitro experiments indicating that translation is directly targeted by oxidative species. In bacteria, these target macromolecules include elongation factors Tu [30][31][32][33][34], Ts (EF-Ts) [32] and G (EF-G) [8,9,22,32,35], several ribosomal proteins [31,36,37], tRNA [38][39][40][41][42] and aminoacyl-tRNA synthetases (aaRS) [31,34,36,37,43,44] (Table 1). rRNA and mRNA has also been shown to be oxidized in vivo in eukaryotes [19,25,26], but in bacteria this has not been tested.…”