| Autor: |
Corson, Laura B., Folmer, Janet, Strain, Jeffrey J., Culotta, Valeria C., Cleveland, Don W. |
| Zdroj: |
Journal of Biological Chemistry; September 1999, Vol. 274 Issue: 39 p27590-27596, 7p |
| Abstrakt: |
The absence of the antioxidant enzyme Cu,Zn-superoxide dismutase (SOD1) is shown here to cause vacuolar fragmentation in Saccharomyces cerevisiae.Wild-type yeast have 1–3 large vacuoles whereas the sod1Δyeast have as many as 50 smaller vacuoles. Evidence that this fragmentation is oxygen-mediated includes the findings that aerobically (but not anaerobically) grown sod1Δyeast exhibit aberrant vacuoles and genetic suppressors of other oxygen-dependentsod1null phenotypes rescue the vacuole defect. Surprisingly, iron also is implicated in the fragmentation process as iron addition exacerbates the sod1Δvacuole defect while iron starvation ameliorates it. Because the vacuole is reported to be a site of iron storage and iron reacts avidly with reactive oxygen species to generate toxic side products, we propose that vacuole damage in sod1Δcells arises from an elevation of iron-mediated oxidation within the vacuole or from elevated pools of “free” iron that may bind nonproductively to vacuolar ligands. Furthermore, additional pleiotropic phenotypes of sod1Δcells (including increased sensitivity to pH, nutrient deprivation, and metals) may be secondary to vacuolar compromise. Our findings support the hypothesis that oxidative stress alters cellular iron homeostasis which in turn increases oxidative damage. Thus, our findings may have medical relevance as both oxidative stress and alterations in iron homeostasis have been implicated in diverse human disease processes. Our findings suggest that strategies to decrease intracellular iron may significantly reduce oxidatively induced cellular damage. |
| Databáze: |
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