Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
Mol Syst Biol. 2011 Nov 8;7:545. doi: 10.1038/msb.2011.80.
Nutrient sensing and coordination of metabolic pathways are crucial functions for all living cells, but details of the coordination under different environmental conditions remain elusive. We therefore undertook a systems biology approach to investigate the interactions between the Snf1 and the target of rapamycin complex 1 (TORC1) in Saccharomyces cerevisiae. We show that Snf1 regulates a much broader range of biological processes compared with TORC1 under both glucose- and ammonium-limited conditions. We also find that Snf1 has a role in upregulating the NADP(+)-dependent glutamate dehydrogenase (encoded by GDH3) under derepressing condition, and therefore may also have a role in ammonium assimilation and amino-acid biosynthesis, which can be considered as a convergence of Snf1 and TORC1 pathways. In addition to the accepted role of Snf1 in regulating fatty acid (FA) metabolism, we show that TORC1 also regulates FA metabolism, likely through modulating the peroxisome and β-oxidation. Finally, we conclude that direct interactions between Snf1 and TORC1 pathways are unlikely under nutrient-limited conditions and propose that TORC1 is repressed in a manner that is independent of Snf1.
营养感应和代谢途径的协调是所有活细胞的关键功能，但在不同环境条件下协调的细节仍然难以捉摸。因此，我们采用系统生物学的方法研究了酿酒酵母中 Snf1 和雷帕霉素靶蛋白复合物 1（TORC1）之间的相互作用。我们发现，与 TORC1 相比，Snf1 在葡萄糖和铵盐限制条件下调节了更广泛的生物学过程。我们还发现，Snf1 在去阻遏条件下对 NADP(+)依赖的谷氨酸脱氢酶（由 GDH3 编码）的上调有作用，因此可能也在铵同化和氨基酸生物合成中发挥作用，这可以被认为是 Snf1 和 TORC1 途径的收敛。除了 Snf1 在调节脂肪酸（FA）代谢中的公认作用外，我们还表明 TORC1 也调节 FA 代谢，可能通过调节过氧化物酶体和β-氧化。最后，我们得出结论，在营养限制条件下，Snf1 和 TORC1 途径之间不太可能存在直接相互作用，并提出 TORC1 的抑制方式与 Snf1 无关。
