Genetic analysis of iron citrate toxicity in yeast: Implications for mammalian iron homeostasis
AUTOR(ES)
Chen, Opal S.
FONTE
National Academy of Sciences
RESUMO
Deletion of the yeast homologue of frataxin, YFH1, results in mitochondrial iron accumulation and respiratory deficiency (petite formation). We used a genetic screen to identify mutants that modify iron-associated defects in respiratory activity in Δyfh1 cells. A deletion in the peroxisomal citrate synthase CIT2 in Δyfh1 cells decreased the rate of petite formation. Conversely, overexpression of CIT2 in Δyfh1 cells increased the rate of respiratory loss. Citrate toxicity in Δyfh1 cells was dependent on iron but was independent of mitochondrial respiration. Citrate toxicity was not restricted to iron-laden mitochondria but also occurred when iron accumulated in cytosol because of impaired vacuolar iron storage. These results suggest that high levels of citrate may promote iron-mediated tissue damage.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=139245Documentos Relacionados
- Mercurial toxicity in yeast: evidence for catabolic pathway inhibition.
- Genetic Control of the Cell Division Cycle in Yeast: V. Genetic Analysis of cdc Mutants
- Nitrogen monoxide-mediated control of ferritin synthesis: Implications for macrophage iron homeostasis
- Genes Affecting the Expression of Cytochrome c in Yeast: Genetic Mapping and Genetic Interactions
- Genetic toxicity of three symmetrical diselenides in yeast
