ROS and hypoxia signaling regulate periodic metabolic arousal during insect dormancy to coordinate glucose, amino acid, and lipid metabolism
ROS and hypoxia signaling regulate periodic metabolic arousal during insect dormancy to coordinate glucose, amino acid, and lipid metabolism
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DOI：
10.1073/pnas.2017603118
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发表时间：
2021-01-05
影响因子：
11.1
通讯作者：
Hahn, Daniel A.
中科院分区：
文献类型：
--
作者：
Chen, Chao;Mahar, Rohit;Hahn, Daniel A.
新陈代谢抑制是动物休眠的一个标志，它促进了整体能量节约。一些滞育昆虫和一些哺乳动物冬眠动物有规律的循环模式，大量的代谢抑制和周期性的觉醒交替，其中代谢率急剧增加。以前的研究，主要是在哺乳动物冬眠动物身上，已经表明周期性唤醒是由有氧线粒体的增加驱动的！新陈代谢和许多与能量新陈代谢相关的分子可预见地在周期性的唤醒周期中波动。然而，目前仍不清楚这些快速代谢变化是如何调节的。我们首次发现，滞育的果蝇蛹在代谢抑制时主要使用厌氧糖酵解，但在周期性唤醒时通过三羧酸循环进行有氧呼吸。滞育蛹也清除厌氧副产物，并再生许多代谢中间产物，在唤醒过程中代谢抑制耗尽，这与哺乳动物冬眠者的模式一致。我们发现，活性氧(ROS)水平的降低会导致代谢觉醒，而ROS的升高会延长代谢抑制的持续时间。我们的数据表明，ROS通过改变两种关键代谢酶丙酮酸脱氢酶和肉碱棕榈酰基转移酶I的活性来调节代谢觉醒的时间，这是通过调节缺氧诱导转录因子(HIF)和腺苷5‘-单磷酸活化蛋白激酶(AMPK)的磷酸化水平来实现的。我们的研究表明，ROS信号调节昆虫滞育系统中的周期性唤醒，这表明ROS对调节休眠中其他类型的代谢周期也可能具有重要意义。
Metabolic suppression is a hallmark of animal dormancy that promotes overall energy savings. Some diapausing insects and some mammalian hibernators have regular cyclic patterns of substantial metabolic depression alternating with periodic arousal where metabolic rates increase dramatically. Previous studies, largely in mammalian hibernators, have shown that periodic arousal is driven by an increase in aerobic mitochondria! metabolism and that many molecules related to energy metabolism fluctuate predictably across periodic arousal cycles. However, it is still not clear how these rapid metabolic shifts are regulated. We first found that diapausing flesh fly pupae primarily use anaerobic glycolysis during metabolic depression but engage in aerobic respiration through the tricarboxylic acid cycle during periodic arousal. Diapausing pupae also clear anaerobic by-products and regenerate many metabolic intermediates depleted in metabolic depression during arousal, consistent with patterns in mammalian hibernators. We found that decreased levels of reactive oxygen species (ROS) induced metabolic arousal and elevated ROS extended the duration of metabolic depression. Our data suggest ROS regulates the timing of metabolic arousal by changing the activity of two critical metabolic enzymes, pyruvate dehydrogenate and carnitine palmitoyltransferase I by modulating the levels of hypoxia inducible transcription factor (HIF) and phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK). Our study shows that ROS signaling regulates periodic arousal in our insect diapasue system, suggesting the possible importance ROS for regulating other types of of metabolic cycles in dormancy as well.