A genetic toolkit for the analysis of metabolic changes in Drosophila provides new insights into metabolic responses to stress and malignant transformation
A genetic toolkit for the analysis of metabolic changes in Drosophila provides new insights into metabolic responses to stress and malignant transformation
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DOI：
10.1038/s41598-019-56446-3
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发表时间：
2019-12-27
影响因子：
4.6
通讯作者：
Wappner, P.
中科院分区：
文献类型：
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作者：
Gandara, L.;Durrieu, L.;Wappner, P.
能量代谢的调节从根本上发生在细胞水平上，因此分析策略必须以达到单细胞分辨率为目标，以完全接受其固有的复杂性。我们已经开发了一套利用代谢FRET传感器的工具集来通过成像技术评估体内果蝇组织中乳酸、丙酮酸和2-氧戊二酸水平的方法。我们在这里展示了低氧是如何改变能量代谢的：虽然一些幼虫组织通过执行代谢切换到乳酸发酵来响应低氧水平，但脂肪体和唾液腺不会改变他们的能量代谢。对肿瘤新陈代谢的分析表明，根据遗传背景的不同，一些肿瘤经历了典型的华宝效应的乳源性开关，而其他肿瘤则不是。这个工具箱允许在体内对遗传操纵的果蝇个体进行发育和生理学研究。
Regulation of the energetic metabolism occurs fundamentally at the cellular level, so analytical strategies must aim to attain single cell resolution to fully embrace its inherent complexity. We have developed methods to utilize a toolset of metabolic FRET sensors for assessing lactate, pyruvate and 2-oxoglutarate levels of Drosophila tissues in vivo by imaging techniques. We show here how the energetic metabolism is altered by hypoxia: While some larval tissues respond to low oxygen levels by executing a metabolic switch towards lactic fermentation, the fat body and salivary glands do not alter their energetic metabolism. Analysis of tumor metabolism revealed that depending on the genetic background, some tumors undergo a lactogenic switch typical of the Warburg effect, while other tumors do not. This toolset allows for developmental and physiologic studies in genetically manipulated Drosophila individuals in vivo.