Metabolic restructuring during energy-limited states: insights from Artemia franciscana embryos and other animals.

Metabolic restructuring during energy-limited states: insights from Artemia franciscana embryos and other animals.
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DOI:
10.1016/j.jinsphys.2011.02.010
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发表时间:
2011-05
影响因子:
2.2
通讯作者:
Toner, Mehmet
Toner, Mehmet
中科院分区:
农林科学3区
文献类型:
--
作者:
Hand, Steven C.;Menze, Michael A.;Borcar, Apu;Patil, Yuvraj;Covi, Joseph A.;Reynolds, Julie A.;Toner, Mehmet

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经历环境损害的动物的许多生命史阶段都会进入发育停滞状态,其特征是细胞增殖减少,同时伴有或不伴有整体新陈代谢的减少。在无脊椎动物中报道的最严重的代谢停滞的情况下,即丰年虫胚胎的无氧静止,细胞内环境的酸化是控制分解代谢和合成代谢下调的主要因素。所观察到的 1.5 单位酸化所需的约 50% 的质子当量来自于细胞内区室释放的离子梯度。从代谢停滞中恢复需要用液泡型 ATP 酶(V-ATP 酶)重新隔离质子。这种机制的显着特点是胚胎细胞能够在细胞内离子梯度消散后存活下来。在许多类似滞育的状态中,代谢减少和随后的能量需求匹配是通过将能量代谢从氧化磷酸化转变为有氧糖酵解来实现的。被激活以诱导这些弹性低代谢状态的分子途径包括刺激 AMP 激活蛋白激酶 (AMPK) 和通过一系列 daf(dauer 形成)基因进行胰岛素信号传导,以实现线虫和昆虫的滞育样状态。其他代谢抑制状态的影响因素包括缺氧诱导因子 1 和丙酮酸脱氢酶复合物的下调。自然停滞状态和一些癌症表型之间的代谢相似性值得注意。通过氧化磷酸化减少通量有助于防止某些癌症类型的细胞死亡,类似于它增加秀丽隐杆线虫多尔阶段活力的方式。自然停滞的机制被用来在细胞生物稳定和储存之前预处理哺乳动物细胞。
Many life history stages of animals that experience environmental insults enter developmental arrested states that are characterized by reduced cellular proliferation, with or without a concurrent reduction in overall metabolism. In the case of the most profound metabolic arrest reported in invertebrates, i.e., anaerobic quiescence in Artemia franciscana embryos, acidification of the intracellular milieu is a major factor governing catabolic and anabolic downregulation. Release of ion gradients from intracellular compartments is the source for approximately 50% of the proton equivalents needed for the 1.5 unit acidification that is observed. Recovery from the metabolic arrest requires re-sequestration of the protons with a vacuolar-type ATPase (V-ATPase). The remarkable facet of this mechanism is the ability of embryonic cells to survive the dissipation of intracellular ion gradients. Across many diapause-like states, the metabolic reduction and subsequent matching of energy demand is accomplished by shifting energy metabolism from oxidative phosphorylation to aerobic glycolysis. Molecular pathways that are activated to induce these resilient hypometabolic states include stimulation of the AMP-activated protein kinase (AMPK) and insulin signaling via suite of daf (dauer formation) genes for diapause-like states in nematodes and insects. Contributing factors for other metabolically-depressed states involve hypoxia-inducible factor-1 and downregulation of the pyruvate dehydrogenase complex. Metabolic similarities between natural states of stasis and some cancer phenotypes are noteworthy. Reduction of flux through oxidative phosphorylation helps prevent cell death in certain cancer types, similar to the way it increases viability of dauer stages in Caenorhabditis elegans. Mechanisms that underlie natural stasis are being used to precondition mammalian cells prior to cell biostabilization and storage.
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