The Pentose Phosphate Pathway Regulates the Circadian Clock.
The Pentose Phosphate Pathway Regulates the Circadian Clock.
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DOI：
10.1016/j.cmet.2016.07.024
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发表时间：
2016-09-13
期刊：
影响因子：
29
通讯作者：
Reddy AB
中科院分区：
文献类型：
--
作者：
Rey G;Valekunja UK;Feeney KA;Wulund L;Milev NB;Stangherlin A;Ansel-Bollepalli L;Velagapudi V;O'Neill JS;Reddy AB
生物钟是一个无处不在的计时系统，它组织生物体在白天和黑夜的行为和生理。目前的模型依赖于转录网络，协调成千上万的转录本的昼夜基因表达。然而，最近的研究已经发现了可独立于转录周期发生的遗传上保守的氧化还原节律。在这里，我们确定戊糖磷酸途径（PPP），氧化还原辅因子NADPH的一个重要来源，作为氧化还原和转录振荡的重要调节器。我们的研究结果表明，PPP的遗传和药理学抑制会影响人类细胞、小鼠组织和果蝇的昼夜节律周期。这些代谢操作还导致昼夜节律基因表达程序的重塑，其涉及昼夜节律转录因子BMAL1和CLOCK以及氧化还原敏感性转录因子NRF2。因此，PPP通过NADPH代谢调节昼夜节律，表明NADPH可用性在昼夜节律计时中起关键作用。戊糖磷酸途径通过NADPH代谢调节昼夜节律振荡抑制戊糖磷酸途径重塑昼夜节律基因表达NRF2连接氧化还原振荡到转录节律戊糖磷酸途径调节改变节律行为和组织时钟目前的生物钟控制模型强调转录网络。在这里，雷伊等人。确定戊糖磷酸途径（PPP），产生NADPH，作为一个重要的调节氧化还原和转录振荡。抑制这种高度保守的代谢途径会影响果蝇、小鼠和人类细胞的昼夜节律。
The circadian clock is a ubiquitous timekeeping system that organizes the behavior and physiology of organisms over the day and night. Current models rely on transcriptional networks that coordinate circadian gene expression of thousands of transcripts. However, recent studies have uncovered phylogenetically conserved redox rhythms that can occur independently of transcriptional cycles. Here we identify the pentose phosphate pathway (PPP), a critical source of the redox cofactor NADPH, as an important regulator of redox and transcriptional oscillations. Our results show that genetic and pharmacological inhibition of the PPP prolongs the period of circadian rhythms in human cells, mouse tissues, and fruit flies. These metabolic manipulations also cause a remodeling of circadian gene expression programs that involves the circadian transcription factors BMAL1 and CLOCK, and the redox-sensitive transcription factor NRF2. Thus, the PPP regulates circadian rhythms via NADPH metabolism, suggesting a pivotal role for NADPH availability in circadian timekeeping. Pentose phosphate pathway regulates circadian oscillations through NADPH metabolism Inhibition of pentose phosphate pathway remodels circadian gene expression NRF2 connects redox oscillations to transcriptional rhythms Pentose phosphate pathway modulation alters rhythmic behavior and tissue clocks Current models of circadian clock control emphasize transcriptional networks. Here, Rey et al. identify the pentose phosphate pathway (PPP), which generates NADPH, as an important regulator of redox and transcriptional oscillations. Inhibition of this highly conserved metabolic pathway affects circadian rhythms in flies, mice, and human cells.
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影响因子：
13.8
作者：
Patra, Krushna C.;Hay, Nissim
通讯作者：
Hay, Nissim
影响因子：
14.9
作者：
Chorley BN;Campbell MR;Wang X;Karaca M;Sambandan D;Bangura F;Xue P;Pi J;Kleeberger SR;Bell DA
通讯作者：
Bell DA
影响因子：
10.5
作者：
Pekovic-Vaughan V;Gibbs J;Yoshitane H;Yang N;Pathiranage D;Guo B;Sagami A;Taguchi K;Bechtold D;Loudon A;Yamamoto M;Chan J;van der Horst GT;Fukada Y;Meng QJ
通讯作者：
Meng QJ
影响因子：
4.5
作者：
Liu AC;Tran HG;Zhang EE;Priest AA;Welsh DK;Kay SA
通讯作者：
Kay SA
DOI：
10.1126/science.1171641
发表时间：
2009-05-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ramsey KM;Yoshino J;Brace CS;Abrassart D;Kobayashi Y;Marcheva B;Hong HK;Chong JL;Buhr ED;Lee C;Takahashi JS;Imai S;Bass J
通讯作者：
Bass J