title: Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal- and glyoxal-glycated cysteine, arginine, and lysine residues.
abstract: Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we show that human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate, respectively. DJ-1 deglycates cysteines, arginines, and lysines (the three major glycated amino acids) of serum albumin, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and aspartate aminotransferase and thus reactivates these proteins. DJ-1 prevented protein glycation in an Escherichia coli mutant deficient in the DJ-1 homolog YajL and restored cell viability in glucose-containing media. These results suggest that DJ-1-associated Parkinsonism results from excessive protein glycation and establishes DJ-1 as a major anti-glycation and anti-aging protein.
authors.affiliation: From the Stress Molecules, Institut Jacques Monod, Université Paris 7, CNRS UMR 7592, 75013 Paris, France, richarme@paris7.jussieu.fr.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Richarme
authors.affiliation: From the Stress Molecules, Institut Jacques Monod, Université Paris 7, CNRS UMR 7592, 75013 Paris, France.
authors.forename: Mouadh
authors.initials: M
authors.lastname: Mihoub
authors.affiliation: the Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative UMR 8251 CNRS, Bioprofiler Facility, F-75205, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
authors.affiliation: the Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative UMR 8251 CNRS, Bioprofiler Facility, F-75205, Paris, France.
authors.forename: Linh Chi
authors.initials: LC
authors.lastname: Bui
authors.affiliation: the Proteomics Facility, Institut Jacques Monod, Université Paris 7, CNRS, UMR 7592, 75013 Paris, France, and.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Leger
authors.affiliation: the Université Paris Diderot, Sorbonne Paris Cite, ITODYS, UMR 7086 CNRS, 75013 Paris, France.
authors.forename: Aazdine
authors.initials: A
authors.lastname: Lamouri
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry; D000418:Albumins / Q000737:chemistry; D017209:Apoptosis; D001120:Arginine / Q000737:chemistry*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002384:Catalysis; D002470:Cell Survival; D003545:Cysteine / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D005947:Glucose / Q000737:chemistry; D006016:Glycolates / Q000737:chemistry; D006037:Glyoxal / Q000737:chemistry*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007773:Lactates / Q000737:chemistry; D008239:Lysine / Q000737:chemistry*; D013058:Mass Spectrometry; D015513:Oncogene Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D020734:Parkinsonian Disorders / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D011765:Pyruvaldehyde / Q000737:chemistry*
chemical_list: D000418:Albumins; D006016:Glycolates; D047908:Intracellular Signaling Peptides and Proteins; D007773:Lactates; D015513:Oncogene Proteins; C031149:glycolic acid; D006037:Glyoxal; D011765:Pyruvaldehyde; D001120:Arginine; D001219:Aspartate Aminotransferases; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D005634:Fructose-Bisphosphate Aldolase; D005947:Glucose; D008239:Lysine; D003545:Cysteine; D000111:Acetylcysteine
keywords: Carbonyl Stress; Dicarbonyl Compounds; Electrophile Stress; Glycation; Protein Aggregation; Protein Chemical Modification; Protein Conformation; Protein Denaturation