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Methionine sulfoxide reductase 2 reversibly regulates Mge1, a cochaperone of mitochondrial Hsp70, during oxidative stress
- Source :
- Molecular Biology of the Cell
- Publication Year :
- 2015
- Publisher :
- The American Society for Cell Biology, 2015.
-
Abstract
- Methionine sulfoxide reductases are important regulators of oxidative stress, as they reduce oxidized methionine in proteins. Mge1, a cochaperone of mtHsp70, is a physiological substrate of Mxr2 and regulates reversibly to maintain mitochondrial protein homeostasis and oxidative stress.<br />Peptide methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in protein(s). Although these reductases have been implicated in several human diseases, there is a dearth of information on the identity of their physiological substrates. By using Saccharomyces cerevisiae as a model, we show that of the two methionine sulfoxide reductases (MXR1, MXR2), deletion of mitochondrial MXR2 renders yeast cells more sensitive to oxidative stress than the cytosolic MXR1. Our earlier studies showed that Mge1, an evolutionarily conserved nucleotide exchange factor of Hsp70, acts as an oxidative sensor to regulate mitochondrial Hsp70. In the present study, we show that Mxr2 regulates Mge1 by selectively reducing MetO at position 155 and restores the activity of Mge1 both in vitro and in vivo. Mge1 M155L mutant rescues the slow-growth phenotype and aggregation of proteins of mxr2Δ strain during oxidative stress. By identifying the first mitochondrial substrate for Mxrs, we add a new paradigm to the regulation of the oxidative stress response pathway.
- Subjects :
- Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae
Oxidative phosphorylation
Biology
Mitochondrion
medicine.disease_cause
Mitochondrial Membrane Transport Proteins
chemistry.chemical_compound
Mitochondrial membrane transport protein
Methionine
medicine
HSP70 Heat-Shock Proteins
Molecular Biology
Cell Biology
Articles
biology.organism_classification
Mitochondria
Cytosol
Oxidative Stress
chemistry
Biochemistry
Cell Biology of Disease
Methionine Sulfoxide Reductases
biology.protein
Methionine sulfoxide reductase
Mutant Proteins
Oxidoreductases
Oxidation-Reduction
Oxidative stress
Molecular Chaperones
Subjects
Details
- Language :
- English
- ISSN :
- 19394586 and 10591524
- Volume :
- 26
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....acf607475bda2742aad15a916f6329d0