Department of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-0861, Japan.
Sci Rep. 2016 Sep 16;6:33536. doi: 10.1038/srep33536.
Peroxiredoxin is an abundant peroxidase, but its non-peroxidase function is also important. In this study, we discovered that Tsa1, a major peroxiredoxin of budding yeast cells, is required for the efficient flux of gluconeogenesis. We found that the suppression of pyruvate kinase (Pyk1) via the interaction with Tsa1 contributes in part to gluconeogenic enhancement. The physical interactions between Pyk1 and Tsa1 were augmented during the shift from glycolysis to gluconeogenesis. Intriguingly, a peroxidatic cysteine in the catalytic center of Tsa1 played an important role in the physical Tsa1-Pyk1 interactions. These interactions are enhanced by exogenous H2O2 and by endogenous reactive oxygen species, which is increased during gluconeogenesis. Only the peroxidatic cysteine, but no other catalytic cysteine of Tsa1, is required for efficient growth during the metabolic shift to obtain maximum yeast growth (biomass). This Tsa1 function is separable from the peroxidase function as an antioxidant. This is the first report to demonstrate that peroxiredoxin has a novel nonperoxidase function as a redox-dependent target modulator and that pyruvate kinase is modulated via an alternative mechanism.
过氧化物酶体是一种丰富的过氧化物酶，但它的非过氧化物酶功能也很重要。在这项研究中，我们发现芽殖酵母细胞中的主要过氧化物酶体 Tsa1 对于糖异生的有效通量是必需的。我们发现，通过与 Tsa1 的相互作用抑制丙酮酸激酶 (Pyk1) 在一定程度上促进了糖异生。在从糖酵解到糖异生的转变过程中，Pyk1 和 Tsa1 之间的物理相互作用增加了。有趣的是，催化中心的过氧物酶半胱氨酸在 Tsa1 与 Pyk1 的物理相互作用中起着重要作用。这些相互作用通过外源性 H2O2 和内源性活性氧物种增强，在糖异生过程中活性氧物种增加。只有过氧物酶半胱氨酸，而不是 Tsa1 的其他催化半胱氨酸，对于在获得最大酵母生长（生物量）的代谢转变过程中进行有效生长是必需的。Tsa1 的这种功能与作为抗氧化剂的过氧化物酶功能是可分离的。这是第一个证明过氧化物酶具有作为氧化还原依赖性靶标调节剂的新的非过氧化物酶功能的报告，并且丙酮酸激酶通过替代机制进行调节。
