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Regulation of mitochondrial thioredoxin peroxidase I expression by two different pathways: one dependent on cAMP and the other on heme   Monteiro, G.; Pereira, G. A. G. and Soares Netto, L. E.  FRBM - Free Radical Biology & Medicine. 32(3): 278-288  2002

Mitochondrial isoform of thioredoxin peroxidase (mTPx I) is an antioxidant protein recently described in Saccharomyces cerevisiae. Here we characterized pathways that lead to mTPx I induction in two situations: growth in media containing low glucose concentrations and treatment with peroxides. The induction of mTPx I by growth on low glucose concentrations was dependent on cAMP and on the transcription factors Msn2p/Msn4p as demonstrated by northern blot experiments using yeast strains with deletion of MSN2 and MSN4 genes and also using a strain permeable to cAMP. mTPx I expression was also induced by peroxides in a time- and dose-dependent manner and varied with the carbon source present in the media. Deletion of HAP1 or inhibition of heme synthesis abolished induction of mTPx I by H2O2 on cells which were grown in media containing glucose, indicating that Hap1p is involved in the regulation of this process. mTPx I was induced by H2O2 on glycerol/ethanol-containing media, but we could not associate any transcription factor with this phenomenon. Finally, mTPx I also induced by t-butyl hydroperoxide in a Hap1p-independent manner. In conclusion, mTPx I expression is under a complex regulatory network, which involves, at least, two signaling pathways: one sensing the carbon source (which is signalized by cAMP) and the other sensing the intracellular redox state (which is signalized by heme).

Apoio financeiro: FAPESP
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