Robust Glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI Family Member
Protein,Is Critical for Oxidative Stress Resistance in Saccharomyces
cerevisiae |
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Authors: | Kondalarao Bankapalli SreeDivya Saladi Sahezeel S. Awadia Arvind Vittal Goswami Madhuja Samaddar Patrick D'Silva |
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Affiliation: | From the Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India |
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Abstract: | Methylglyoxal (MG) is a reactive metabolic intermediate generated during variouscellular biochemical reactions, including glycolysis. The accumulation of MGindiscriminately modifies proteins, including important cellular antioxidantmachinery, leading to severe oxidative stress, which is implicated in multipleneurodegenerative disorders, aging, and cardiac disorders. Although cellspossess efficient glyoxalase systems for detoxification, their functions arelargely dependent on the glutathione cofactor, the availability of which isself-limiting under oxidative stress. Thus, higher organisms require alternatemodes of reducing the MG-mediated toxicity and maintaining redox balance. Inthis report, we demonstrate that Hsp31 protein, a member of the ThiJ/DJ-1/PfpIfamily in Saccharomyces cerevisiae, plays an indispensable rolein regulating redox homeostasis. Our results show that Hsp31 possesses robustglutathione-independent methylglyoxalase activity and suppresses MG-mediatedtoxicity and ROS levels as compared with another paralog, Hsp34. On the otherhand, glyoxalase-defective mutants of Hsp31 were found highly compromised inregulating the ROS levels. Additionally, Hsp31 maintains cellular glutathioneand NADPH levels, thus conferring protection against oxidative stress, and Hsp31relocalizes to mitochondria to provide cytoprotection to the organelle underoxidative stress conditions. Importantly, human DJ-1, which is implicated in thefamilial form of Parkinson disease, complements the function of Hsp31 bysuppressing methylglyoxal and oxidative stress, thus signifying the importanceof these proteins in the maintenance of ROS homeostasis across phylogeny. |
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Keywords: | heat shock protein (HSP) mitochondria mitochondrial transport molecular chaperone oxidative stress Parkinson disease protein folding yeast genetics |
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