Robust Glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI Family Member Protein, Is Critical for Oxidative Stress Resistance in Saccharomyces cerevisiae

• Published in: The Journal of biological chemistry Vol. 290; no. 44; pp. 26491 - 26507
• Main Authors: Bankapalli, Kondalarao, Saladi, SreeDivya, Awadia, Sahezeel S., Goswami, Arvind Vittal, Samaddar, Madhuja, D'Silva, Patrick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.10.2015; American Society for Biochemistry and Molecular Biology
• Subjects: heat shock protein (HSP); Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Humans; Lactoylglutathione Lyase - genetics; Lactoylglutathione Lyase - metabolism; mitochondria; Mitochondria - enzymology; Mitochondria - genetics; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; mitochondrial transport; molecular chaperone; Mutation; NADP - genetics; NADP - metabolism; oxidative stress; Oxidative Stress - physiology; Parkinson disease; protein folding; Protein Structure and Folding; Protein Transport - physiology; Pyruvaldehyde - metabolism; Reactive Oxygen Species - metabolism; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; yeast genetics; molecular chaperone; yeast genetics; mitochondria; mitochondrial transport; Parkinson disease; protein folding; oxidative stress; heat shock protein (HSP)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M115.673624

Methylglyoxal (MG) is a reactive metabolic intermediate generated during various cellular biochemical reactions, including glycolysis. The accumulation of MG indiscriminately modifies proteins, including important cellular antioxidant machinery, leading to severe oxidative stress, which is implicated in multiple neurodegenerative disorders, aging, and cardiac disorders. Although cells possess efficient glyoxalase systems for detoxification, their functions are largely dependent on the glutathione cofactor, the availability of which is self-limiting under oxidative stress. Thus, higher organisms require alternate modes of reducing the MG-mediated toxicity and maintaining redox balance. In this report, we demonstrate that Hsp31 protein, a member of the ThiJ/DJ-1/PfpI family in Saccharomyces cerevisiae, plays an indispensable role in regulating redox homeostasis. Our results show that Hsp31 possesses robust glutathione-independent methylglyoxalase activity and suppresses MG-mediated toxicity and ROS levels as compared with another paralog, Hsp34. On the other hand, glyoxalase-defective mutants of Hsp31 were found highly compromised in regulating the ROS levels. Additionally, Hsp31 maintains cellular glutathione and NADPH levels, thus conferring protection against oxidative stress, and Hsp31 relocalizes to mitochondria to provide cytoprotection to the organelle under oxidative stress conditions. Importantly, human DJ-1, which is implicated in the familial form of Parkinson disease, complements the function of Hsp31 by suppressing methylglyoxal and oxidative stress, thus signifying the importance of these proteins in the maintenance of ROS homeostasis across phylogeny. Background: ThiJ/DJ-1/PfpI protein family members possess glutathione-independent glyoxalase activity. Results:S. cerevisiae Hsp31, an efficient glyoxalase among all paralogs is essential for cytoprotection under oxidative stress conditions. Conclusion: The robust glyoxalase activity of Hsp31 aids in the maintenance of glutathione levels, and its mitochondrial localization provides protection against oxidative stress. Significance: This is the first demonstration of the mechanisms of ThiJ/DJ-1/PfpI family in combating oxidative stress in yeast.