Reference: Li L, et al. (2010) Genetic dissection of a mitochondria-vacuole signaling pathway in yeast reveals a link between chronic oxidative stress and vacuolar iron transport. J Biol Chem 285(14):10232-42

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Abstract


Deletion of two homologous genes MRS3 and MRS4 that encode mitochondrial iron transporters affects the activity of the vacuolar iron importer Ccc1. Ccc1 levels are decreased in mrs3mrs4 cells but the activity of the transporter is increased, resulting is reduced cytosolic iron. Overexpression of CCC1 in mrs3mrs4 cells results in a severe growth defect due to decreased cytosolic iron, referred to as the Mitochondria Vacuolar Signaling (MVS) phenotype. Mutants were identified that suppress the MVS growth defect and FRA1 was identified as a gene that suppresses the MVS phenotype. Overexpression of FRA1 suppresses altered transition metal metabolism in mrs3mrs4 cells, while deletion of FRA1 is synthetically lethal with mrs3mrs4. Fra1 binds to Tsa1, which encodes a thioredoxin-dependent peroxidase. Deletion of TSA1 or TRR1 is synthetically lethal in mrs3mrs4 cells, suggesting that mrs3mrs4 cells are generating reactive oxygen metabolites. The generation of reactive oxygen metabolites in mrs3mrs4 cells was confirmed by use of the reporter molecule dichlorodihydrofluorescein diacetate (DCFDA). These results suggest that mitochondrial induced oxidant damage is responsible for activating Ccc1 and that Fra1 and Tsa1 can reduce oxidant damage.

Reference Type
Journal Article
Authors
Li L, Murdock G, Bagley D, Jia X, Mc Vey Ward D, Kaplan J
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