Grx5p : a mitochondrial glutaredoxin required for mitochondrial DNA maintenance
(2005)
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- Authors
- Supervisors
- Foury, Françoise
- Abstract
- Mitochondria are a major site of production of reactive oxygen species (ROS) such as hydrogen peroxide, superoxide anion and hydroxyl radical. To protect against oxidative damages, cells have developed scavenging systems including proteins and small molecules. A major detoxification role is played by the glutathione/glutaredoxin and thioredoxin systems. These systems are present in both cytosol and mitochondria of all respiring organisms, and in particular Saccharomyces cerevisiae. The exact function of scavengers remains unclear. The following genes encoding yeast mitochondrial scavenging proteins have been deleted alone or in combination, TRX3 (thioredoxin 3), TRR1 (thioredoxin reductase 1), GRX5 (glutaredoxin 5), SOD2 (Mn-superoxide dismutase) and PRX1 (peroxiredoxin 1). Deleted strains have been shown to exhibit mild phenotypes except the strain deleted for GRX5 (∆GRX5). This mutant exhibits increased sensitivity to hydrogen peroxide, menadione and transition metals such as copper and iron. These data show that Grx5p plays a role in cell redox homeostasis. This work has confirmed that Grx5p plays a role in biosynthesis of the Fe-S clusters. Iron accumulates in ∆GRX5 mitochondria and the activity of aconitase, a mitochondrial [4Fe-4S] cluster enzyme is extremely low. In contrast with another report, we did not find high iron levels in the cytosol. Aconitase has been shown to be highly sensitive to proteolysis in ∆GRX5 strain, suggesting that the apo-protein is recognized by the Pim1p quality control protease. Using genetics and optic microscopy, we have shown that GRX5 deletion leads to total loss of wild type mitochondrial DNA and to extreme instability of rho- genomes. We propose that mitochondrial iron overload, resulting from defects in Fe-S cluster synthesis, associated with loss of the oxido-reductase activity is responsible for all the phenotypes of the ∆GRX5 strain. This PhD work was supported by a grant from European Union (MitAGE contract: QLK6-CT-2000-00054) ...
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Citations
Trincal, M. (2005). Grx5p : a mitochondrial glutaredoxin required for mitochondrial DNA maintenance. https://hdl.handle.net/2078.5/98472