Iron deficiency leads to repression of a non-canonical methionine salvage pathway in Schizosaccharomyces pombe |
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Authors: | Ariane Brault Simon Labbé |
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Institution: | Département de Biochimie et de Génomique Fonctionnelle, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada |
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Abstract: | The methionine salvage pathway (MSP) regenerates methionine from 5′-methylthioadenosine (MTA). Aerobic MSP consists of six enzymatic steps. The mug14+ and adi1+ genes that are involved in the third and fifth steps of the pathway are repressed when Schizosaccharomyces pombe undergoes a transition from high- to low-iron conditions. Results consistently show that methionine auxotrophic cells (met6Δ) require iron for growth in the presence of MTA as the sole source of methionine. Inactivation of the iron-using protein Adi1 leads to defects in the utilization of MTA. In the case of the third step of the pathway, co-expression of two distinct proteins, Mta3 and Mde1, is required. These proteins are interdependent to rescue MTA-dependent growth deficit of met6Δ cells. Coimmunoprecipitation experiments showed that Mta3 is a binding partner of Mde1. Meiotic met6Δ cells co-expressing mta3+ and mde1+ or mta3+ and mug14+ produce comparable levels of spores in the presence of MTA, revealing that Mde1 and Mug14 share a common function when co-expressed with Mta3 in sporulating cells. In sum, our findings unveil several novel features of MSP, especially with respect to its regulation by iron and the discovery of a non-canonical third enzymatic step in the fission yeast. |
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Keywords: | fission yeast Iron iron economy metabolic response methionine salvage pathway yeast physiology |
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