Kwolek-Mirek Magdalena, Maslanka Roman, Bednarska Sabina, Szczypek Joanna, Baran Justyna, Przywara Michał, Janeczko Agnieszka, Zadrag-Tecza Renata
Faculty of Biology, Nature Protection, and Sustainable Development, University of Rzeszów, 35-601 Rzeszów, Poland.
Int J Mol Sci. 2025 Sep 17;26(18):9047. doi: 10.3390/ijms26189047.
The maintenance of intracellular redox homeostasis depends on the GSH/GSSG pair, which is the primary intracellular redox buffer. However, the NADPH/NADP pair also plays a vital role in this process. The primary source of NADPH is the pentose phosphate pathway and deficiency in the enzymes responsible for NADPH production in this pathway leads to developing of alternative NADPH supply strategies. The choice of compensation strategy has several consequences for cells physiology. The present study investigates how yeast strains defective in generating NADPH via the pentose phosphate pathway due to deletion of , , or genes, respond to redox homeostasis disruption caused by allyl alcohol, a metabolic precursor of acrolein. Acrolein is a highly reactive aldehyde that rapidly depletes glutathione and triggers oxidative stress. Therefore, cells respond to acrolein through attempts to increase glutathione synthesis, but also by increasing NADPH production. The response requires coordinated action of glutathione- and NADPH-dependent systems. The high sensitivity of the Δ strain, which is unable to activate an adequate stress response, is evidence of this. The strategy employed by this strain to maintain redox homeostasis is inadequate and may even exacerbate allyl alcohol toxicity.
细胞内氧化还原稳态的维持依赖于谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）对，这是细胞内主要的氧化还原缓冲剂。然而，烟酰胺腺嘌呤二核苷酸磷酸/还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH/NADP）对在这一过程中也起着至关重要的作用。NADPH的主要来源是磷酸戊糖途径，该途径中负责NADPH生成的酶缺乏会导致替代NADPH供应策略的发展。补偿策略的选择对细胞生理学有若干影响。本研究调查了由于删除、或基因而在通过磷酸戊糖途径生成NADPH方面存在缺陷的酵母菌株，如何应对由烯丙醇（丙烯醛的代谢前体）引起的氧化还原稳态破坏。丙烯醛是一种高反应性醛，它会迅速消耗谷胱甘肽并引发氧化应激。因此，细胞通过尝试增加谷胱甘肽合成来应对丙烯醛，同时也通过增加NADPH生成来应对。这种反应需要谷胱甘肽依赖性和NADPH依赖性系统的协同作用。Δ菌株无法激活适当的应激反应，其高敏感性证明了这一点。该菌株用于维持氧化还原稳态的策略是不充分的，甚至可能加剧烯丙醇的毒性。
