Mary Ann Liebert, Antioxidants and Redox Signaling, 10(24), p. 543-547, 2016
Full text: Download
Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a ROS scavenger, methionine is implicated in caloric restriction phenotypes and ageing. We here provide evidence that some effects of methionine in stress situations are indirect, and caused by altered activity of the NADPH producing, oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae , both methionine prototrophic ( MET15 ) and auxotrophic (met15∆ ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase (6PGDH). Proteomics revealed this enzyme to also increase in expression compared to non-treated cells. Oxidant tolerance was also increased in cells pre-incubated with methionine, however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1 . Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signalling and ageing have thus to be seen in the context of an altered activity of this NADP reducing pathway.