Cell cycle progression is regulated by intertwined redox oscillators.

Cell cycle progression is regulated by intertwined redox oscillators.
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DOI:
10.1186/s12976-015-0005-2
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发表时间:
2015-05-29
影响因子:
--
通讯作者:
Schwartz L
Schwartz L
中科院分区:
生物学4区
文献类型:
--
作者:
da Veiga Moreira J;Peres S;Steyaert JM;Bigan E;Paulevé L;Nogueira ML;Schwartz L

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真核细胞周期的不同阶段是保存异常完好的现象。DNA解压缩、RNA和蛋白质合成(在G1期晚期),随后是DNA复制(在S期)和脂质合成(在G2期),发生在静息细胞(在G 0期)致力于增殖之后。细胞周期的G1期的特征在于糖酵解代谢的增加,由高NAD+/NADH比率维持。可能由于乳酸合成或ATP水解,发生短暂的胞质酸化,随后发生胞质碱化。由于钠/钾泵(NaK-ATP酶)活性,还观察到超极化跨膜电位。在细胞周期的进展过程中,戊糖磷酸途径(PPP)被NADP+/NADPH比率增加激活,将葡萄糖6-磷酸转化为核苷酸前体。然后,核酸合成和DNA复制发生在S期。沿着S期,未发表的结果显示细胞溶质酸化,可能是在该阶段发生的精氨酸分解的结果。在G2期,NADPH浓度(用于膜脂质合成)降低,细胞质发生碱化。线粒体过度融合与G1/S转换后期的胞质酸化相匹配,然后通过氧化磷酸化触发ATP合成。我们在这里假设,细胞溶质的pH值可能协调线粒体的活性,从而不同的氧化还原循环,这反过来又控制细胞代谢。
The different phases of the eukaryotic cell cycle are exceptionally well-preserved phenomena. DNA decompaction, RNA and protein synthesis (in late G1 phase) followed by DNA replication (in S phase) and lipid synthesis (in G2 phase) occur after resting cells (in G0) are committed to proliferate. The G1 phase of the cell cycle is characterized by an increase in the glycolytic metabolism, sustained by high NAD+/NADH ratio. A transient cytosolic acidification occurs, probably due to lactic acid synthesis or ATP hydrolysis, followed by cytosolic alkalinization. A hyperpolarized transmembrane potential is also observed, as result of sodium/potassium pump (NaK-ATPase) activity. During progression of the cell cycle, the Pentose Phosphate Pathway (PPP) is activated by increased NADP+/NADPH ratio, converting glucose 6-phosphate to nucleotide precursors. Then, nucleic acid synthesis and DNA replication occur in S phase. Along with S phase, unpublished results show a cytosolic acidification, probably the result of glutaminolysis occurring during this phase. In G2 phase there is a decrease in NADPH concentration (used for membrane lipid synthesis) and a cytoplasmic alkalinization occurs. Mitochondria hyperfusion matches the cytosolic acidification at late G1/S transition and then triggers ATP synthesis by oxidative phosphorylation. We hypothesize here that the cytosolic pH may coordinate mitochondrial activity and thus the different redox cycles, which in turn control the cell metabolism.
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