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Cross-compartment protection by SOD1.
Stefan I Liochev1, Irwin Fridovich
1Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, NC 27710, USA.
Free Radical Biology & Medicine
|December 14, 2004
Summary
Yeast lacking superoxide dismutase 1 (SOD1) show lysine auxotrophy due to mitochondrial enzyme inactivation. We propose peroxynitrite formation explains this SOD1-independent inactivation of Lys4p.
Area of Science:
- Biochemistry
- Cell Biology
- Mitochondrial Biology
Background:
- Lysine biosynthesis involves the [4Fe-4S]-containing dehydratase Lys4p.
- Absence of superoxide dismutase 1 (SOD1) in yeast leads to Lys4p inactivation and lysine auxotrophy.
- SOD1 is located in the cytosol and mitochondrial intermembrane space, while Lys4p is in the mitochondrial matrix.
Purpose of the Study:
- To investigate the mechanism of Lys4p inactivation in yeast lacking SOD1.
- To explain how SOD1, localized outside the mitochondrial matrix, can protect matrix-localized Lys4p.
Main Methods:
- Comparative analysis of enzyme activity in wild-type and SOD1-deficient yeast strains.
- Hypothesizing reactive nitrogen species involvement based on subcellular localization and known chemical reactions.
Main Results:
- SOD1 absence results in oxygen-dependent lysine auxotrophy.
- A proposed mechanism involves cytosolic/intermembrane reactive oxygen species (ROS) reacting with nitric oxide (NO) to form peroxynitrite (HOONO).
- Peroxynitrite diffuses into the mitochondrial matrix, inactivating Lys4p and other [4Fe-4S]-containing dehydratases.
Conclusions:
- The study proposes a novel mechanism for oxidative damage to mitochondrial enzymes in the absence of cytosolic/intermembrane SOD1.
- Peroxynitrite formation and diffusion are suggested as the key mediators of Lys4p inactivation.
- This finding highlights indirect protective roles of SOD1 against mitochondrial damage.