期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：26
页码：16922-16927
DOI：10.1073/pnas.232392299
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 {Delta}yfh1 cells. A deletion in the peroxisomal citrate synthase CIT2 in {Delta}yfh1 cells decreased the rate of petite formation. Conversely, overexpression of CIT2 in {Delta}yfh1 cells increased the rate of respiratory loss. Citrate toxicity in {Delta}yfh1 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.
