Robust Glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI Family Member Protein, Is Critical for Oxidative Stress Resistance in Saccharomyces cerevisiae
| Autor: | Kondalarao Bankapalli, Madhuja Samaddar, Patrick D'Silva, Arvind Vittal Goswami, Sahezeel Awadia, SreeDivya Saladi |
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| Rok vydání: | 2015 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Antioxidant medicine.medical_treatment Saccharomyces cerevisiae Mitochondrion medicine.disease_cause Biochemistry Mitochondrial Proteins chemistry.chemical_compound Lactoylglutathione lyase medicine Humans Molecular Biology Heat-Shock Proteins Mitochondrial transport biology Methylglyoxal Lactoylglutathione Lyase Cell Biology Glutathione Pyruvaldehyde Cytoprotection Mitochondria Cell biology Oxidative Stress Protein Transport chemistry Protein Structure and Folding Mutation biology.protein Reactive Oxygen Species NADP Oxidative stress |
| Zdroj: | Journal of Biological Chemistry. 290:26491-26507 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.673624 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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