Metabolic activity alternates between high and low states during different stages of an organism’s life cycle. During the transition from growth to quiescence, a major metabolic shift often occurs from oxidative phosphorylation to glycolysis and gluconeogenesis. We use the entry of Caenorhabditis elegans into the dauer larval stage, a developmentally arrested stage formed in response to harsh environmental conditions, as a model to study the global metabolic changes and underlying molecular mechanisms associated with growth to quiescence transition. Here, we show that the metabolic switch involves the concerted activity of several regulatory pathways. Whereas the steroid hormone receptor DAF-12 controls dauer morphogenesis, the insulin pathway maintains low energy expenditure through DAF-16/FoxO, which also requires AAK-2/AMPKα. DAF-12 and AAK-2 separately promote a shift in the molar ratios between competing enzymes at two key branch points within the central carbon metabolic pathway diverting carbon atoms from the TCA cycle and directing them to gluconeogenesis. When both AAK-2 and DAF-12 are suppressed, the TCA cycle is active and the developmental arrest is bypassed. The metabolic status of each developmental stage is defined by stoichiometric ratios within the constellation of metabolic enzymes driving metabolic flux and controls the transition between growth and quiescence.

中文翻译：

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代谢转换调节线虫的生长和滞育之间的过渡

在生物生命周期的不同阶段，代谢活动在高状态和低状态之间交替变化。在从生长到静止的过渡过程中，通常发生主要的代谢转变，从氧化磷酸化到糖酵解和糖异生。我们使用秀丽隐杆线虫进入dauer幼虫阶段（响应恶劣的环境条件而形成的发育停滞阶段）作为模型来研究全球代谢变化和与生长向静止过渡相关的潜在分子机制的模型。在这里，我们表明代谢转换涉及几个调节途径的协同活动。类固醇激素受体DAF-12控制dauer形态发生，而胰岛素途径通过DAF-16 / FoxO维持低能量消耗，而DAF-16 / FoxO也需要AAK-2 /AMPKα。DAF-12和AAK-2分别促进中心碳代谢途径中两个关键分支点上竞争酶之间摩尔比的变化，从而使TCA循环中的碳原子转移并将其引导至糖异生。当同时抑制了AAK-2和DAF-12时，TCA循环就会激活，而发育停滞则被绕开。每个发育阶段的代谢状态由驱动代谢通量并控制生长和静止之间的过渡的代谢酶群内的化学计量比定义。TCA周期活跃且发育停滞被绕开。每个发育阶段的代谢状态由驱动代谢通量并控制生长和静止之间的过渡的代谢酶群内的化学计量比定义。TCA周期活跃且发育停滞被绕开。每个发育阶段的代谢状态由驱动代谢通量并控制生长和静止之间的过渡的代谢酶群内的化学计量比定义。