Kinetic control by limiting glutaredoxin amounts enables thiol oxidation in the reducing mitochondrial intermembrane space
| Autor: | Johannes M. Herrmann, Gaetano Calabrese, Jan Riemer, Valentina Peleh, Kerstin Kojer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Mitochondrial intermembrane space Biosynthesis and Biodegradation Immunoblotting Saccharomyces cerevisiae Mitochondrion Mitochondrial Membrane Transport Proteins Mitochondrial Proteins chemistry.chemical_compound Mitochondrial membrane transport protein Cytosol Glutaredoxin Mitochondrial Precursor Protein Import Complex Proteins Sulfhydryl Compounds Molecular Biology Glutaredoxins biology Glutathione Disulfide Oxidative folding Glutaredoxin 2 Cell Biology Glutathione Articles Cell biology Mitochondria Kinetics Protein Transport chemistry Mitochondrial Membranes Mutation biology.protein Metalloproteases Glutathione disulfide Oxidation-Reduction Molecular Chaperones |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Proteins of the mitochondrial intermembrane space are oxidatively folded by the incorporation of structural disulfide bonds. Efficient protein oxidation in this highly reducing compartment is possible only because glutaredoxins, which could translate the glutathione redox potential into that of protein thiols, are present at limiting levels. The mitochondrial intermembrane space (IMS) harbors an oxidizing machinery that drives import and folding of small cysteine-containing proteins without targeting signals. The main component of this pathway is the oxidoreductase Mia40, which introduces disulfides into its substrates. We recently showed that the IMS glutathione pool is maintained as reducing as that of the cytosol. It thus remained unclear how equilibration of protein disulfides with the IMS glutathione pool is prevented in order to allow oxidation-driven protein import. Here we demonstrate the presence of glutaredoxins in the IMS and show that limiting amounts of these glutaredoxins provide a kinetic barrier to prevent the thermodynamically feasible reduction of Mia40 substrates by the IMS glutathione pool. Moreover, they allow Mia40 to exist in a predominantly oxidized state. Consequently, overexpression of glutaredoxin 2 in the IMS results in a more reduced Mia40 redox state and a delay in oxidative folding and mitochondrial import of different Mia40 substrates. Our findings thus indicate that carefully balanced glutaredoxin amounts in the IMS ensure efficient oxidative folding in the reducing environment of this compartment. |
| Databáze: | OpenAIRE |
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