Cellular Biochemistry, Technische Universität Kaiserslautern, Kaiserslautern, Germany.
Institute of Biochemistry, Centre for Human and Molecular Biology (ZHMB), Saarland University, Saarbrücken, Germany.
Nat Chem Biol. 2021 Apr;17(4):477-484. doi: 10.1038/s41589-020-00728-9. Epub 2021 Feb 11.
Redox cycles have been reported in ultradian, circadian and cell cycle-synchronized systems. Redox cycles persist in the absence of transcription and cyclin-CDK activity, indicating that cells harbor multiple coupled oscillators. Nonetheless, the causal relationships and molecular mechanisms by which redox cycles are embedded within ultradian, circadian or cell division cycles remain largely elusive. Yeast harbor an ultradian oscillator, the yeast metabolic cycle (YMC), which comprises metabolic/redox cycles, transcriptional cycles and synchronized cell division. Here, we reveal the existence of robust cycling of HO and peroxiredoxin oxidation during the YMC and show that peroxiredoxin inactivation disrupts metabolic cycling and abolishes coupling with cell division. We find that thiol-disulfide oxidants and reductants predictably modulate the switching between different YMC metabolic states, which in turn predictably perturbs cell cycle entry and exit. We propose that oscillatory HO-dependent protein thiol oxidation is a key regulator of metabolic cycling and its coordination with cell division.
氧化还原循环已在超昼夜、昼夜和细胞周期同步系统中报道。氧化还原循环在没有转录和细胞周期蛋白激酶活性的情况下仍然存在，这表明细胞内存在多个耦合振荡器。尽管如此，氧化还原循环如何嵌入超昼夜、昼夜或细胞分裂周期的因果关系和分子机制在很大程度上仍难以捉摸。酵母中存在一个超昼夜振荡器，即酵母代谢周期（YMC），它由代谢/氧化还原循环、转录循环和细胞分裂同步组成。在这里，我们揭示了在 YMC 期间 HO 和过氧化物酶氧化的强循环的存在，并表明过氧化物酶失活会破坏代谢循环并消除与细胞分裂的偶联。我们发现，巯基-二硫键氧化剂和还原剂可预测性地调节不同 YMC 代谢状态之间的转换，这反过来又可预测性地干扰细胞周期的进入和退出。我们提出，依赖 HO 的蛋白巯基氧化的振荡是代谢循环及其与细胞分裂协调的关键调节剂。
