Iron deficiency leads to repression of a non‐canonical methionine salvage pathway in Schizosaccharomyces pombe. Issue 1 (9th March 2020)

• Record Type: Journal Article
• Authors: Brault, Ariane; Labbé, Simon
• Is Part Of: Molecular microbiology. Volume 114:Issue 1(2020)
• Page Start: 46
• Page End: 65
• Publication Date: 2020-03-09
• Subjects: fission yeast -- Iron -- iron economy -- metabolic response -- methionine salvage pathway -- yeast physiology; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14495
• Languages: English
• ISSNs: 0950-382X

Abstract

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. Abstract : The methionine salvage pathway (MSP) is initiated by 5‐methylthioadenosine (MTA) and consists of six enzymatic reactions that serve to regenerate methionine. Under low‐iron conditions, Adi1 and Mug14 are negatively regulated by Php4 in cells growing mitotically and cells undergoing meiotic division respectively. Furthermore, the iron‐dependent MSP includes a non‐canonical third enzymatic step that requires two functionally interdependent proteins during mitosis (Mta3 and Mde1) and meiosis (Mta3 and Mug14).