Institute for Integrative Systems Biology, I2SysBio, University of Valencia-CSIC, Valencia, Spain.
Sci Rep. 2018 Nov 7;8(1):16500. doi: 10.1038/s41598-018-34908-4.
The thioredoxin system plays a predominant role in the control of cellular redox status. Thioredoxin reductase fuels the system with reducing power in the form of NADPH. The TORC1 complex promotes growth and protein synthesis when nutrients, particularly amino acids, are abundant. It also represses catabolic processes, like autophagy, which are activated during starvation. We analyzed the impact of yeast cytosolic thioredoxin reductase TRR1 deletion under different environmental conditions. It shortens chronological life span and reduces growth in grape juice fermentation. TRR1 deletion has a global impact on metabolism during fermentation. As expected, it reduces oxidative stress tolerance, but a compensatory response is triggered, with catalase and glutathione increasing. Unexpectedly, TRR1 deletion causes sensitivity to the inhibitors of the TORC1 pathway, such as rapamycin. This correlates with low Tor2p kinase levels and indicates a direct role of Trr1p in its stability. Markers of TORC1 activity, however, suggest increased TORC1 activity. The autophagy caused by nitrogen starvation is reduced in the trr1Δ mutant. Ribosomal protein Rsp6p is dephosphorylated in the presence of rapamycin. This dephosphorylation diminishes in the TRR1 deletion strain. These results show a complex network of interactions between thioredoxin reductase Trr1p and the processes controlled by TOR.
硫氧还蛋白系统在控制细胞氧化还原状态方面起着主要作用。硫氧还蛋白还原酶以 NADPH 的形式为该系统提供还原能力。当营养物质，特别是氨基酸丰富时，TORC1 复合物促进生长和蛋白质合成。它还抑制分解代谢过程，如自噬，自噬在饥饿时被激活。我们分析了在不同环境条件下酵母胞质硫氧还蛋白还原酶 TRR1 缺失的影响。它缩短了酵母的时序寿命并降低了在葡萄汁发酵中的生长速度。TRR1 缺失对发酵过程中的代谢有全局影响。正如预期的那样，它降低了氧化应激耐受性，但会触发代偿反应，过氧化氢酶和谷胱甘肽增加。出乎意料的是，TRR1 缺失会导致对 TORC1 途径抑制剂（如雷帕霉素）的敏感性。这与 Tor2p 激酶水平降低相关，并表明 Trr1p 在其稳定性中起着直接作用。然而，TORC1 活性的标志物表明 TORC1 活性增加。氮饥饿引起的自噬在 trr1Δ 突变体中减少。核糖体蛋白 Rsp6p 在雷帕霉素存在下去磷酸化。这种去磷酸化在 TRR1 缺失菌株中减少。这些结果表明硫氧还蛋白还原酶 Trr1p 与 TOR 控制的过程之间存在复杂的相互作用网络。
