Laboratory for Growth Control Signaling, RIKEN Center for Biosystems Dynamics Research (BDR), 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Curr Biol. 2020 Sep 21;30(18):3624-3632.e5. doi: 10.1016/j.cub.2020.06.043. Epub 2020 Jul 16.
Metabolism must be coupled with developmental transition to fulfill the energy requirements during an organism's life cycle. In most animals, steroid hormones are crucial regulators of life-stage transitions until adulthood. In the fruit fly Drosophila, ecdysteroid titers drive developmental transitions, such as molting and metamorphosis [1-4]. Although the timings of molting and larval-pupal transition are dependent on environmental and internal conditions, metamorphosis is a temporally controlled life transition event that solely relies on energetic macromolecules accumulated during the larval period. The ecdysteroid signaling cascade and the energetics of metamorphosis have been determined [5-8]. However, the molecular mechanisms that regulate metabolic homeostasis during metamorphosis remain largely unknown. Here, I show that the programmed regulation of carbohydrate metabolism by steroid hormones directs the prepupal-pupal transition in Drosophila. I found that pupation is associated with a transient increase in glucose oxidation. Mechanistically, after pupariation, ecdysteroid signaling and the competence factor Ftz-F1 regulates the systematic degradation of circulating trehalose via the transient induction of trehalose transporters and trehalase (Treh) in a timely manner. Trehalose metabolism is crucial for energy homeostasis at the prepupal-pupal transition. Moreover, trehalose catabolism acts upstream of ecdysteroid biosynthesis and signaling. My findings lead to the hypothesis that trehalose breakdown not only defines energy costs by providing a carbon source but also facilitates pupation by inducing water loss in the puparium. My work sheds light on the ways in which a life-stage transition is driven by the preprogrammed coordination between steroid hormones and catabolism of stored nutrients.
新陈代谢必须与发育转变相耦合，以满足生物体生命周期中的能量需求。在大多数动物中，类固醇激素是生命阶段转变直至成年的关键调节物。在果蝇中，蜕皮激素水平驱动着发育转变，如蜕皮和变态[1-4]。虽然蜕皮和幼虫-蛹转变的时间取决于环境和内部条件，但变态是一个依赖于能量大分子在幼虫期积累的时间控制的生命转变事件。蜕皮激素信号级联和变态的能量学已经确定[5-8]。然而，调节变态期间代谢平衡的分子机制在很大程度上仍然未知。在这里，我表明类固醇激素对碳水化合物代谢的程序化调节指导了果蝇的预蛹-蛹转变。我发现化蛹与葡萄糖氧化的短暂增加有关。从机制上讲，在蛹化后，蜕皮激素信号和功能因子 Ftz-F1 通过瞬态诱导海藻糖转运蛋白和海藻糖酶（Treh）来调节循环海藻糖的系统降解，从而及时发挥作用。海藻糖代谢对于预蛹-蛹转变期间的能量平衡至关重要。此外，海藻糖分解代谢作用于蜕皮激素生物合成和信号的上游。我的发现导致了这样一种假设，即海藻糖分解不仅通过提供碳源来定义能量成本，而且通过在蛹壳中诱导水分流失来促进化蛹。我的工作揭示了生命阶段转变是如何通过类固醇激素和储存营养物质分解代谢之间的预编程协调来驱动的。
