A genetic toolkit for the analysis of metabolic changes in Drosophila provides new insights into metabolic responses to stress and malignant transformation

BEHRENSEN, C.; WAPPNER, P.; GÁNDARA, L.; DURRIEU, L.

Ciudad de Buenos Aires

Congreso; Xth Meeting of the Latin American Society for Developmental Biology; 2019

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 environmental cues in wing imaginal discs. Besides, we found that larval tissues that contribute directly to adult organs respond to oxygen deprivation (hypoxia) differently from the polytene tissues degraded during metamorphosis. Whilst the first group engages in a metabolic rewiring that leads to lactate accumulation, polytene tissues do not alter their lactate levels in hypoxia. We also altered the lactate concentration in a restricted domain of wing discs by genetic manipulation of key metabolic enzymes, proving that these tools are suitable to be used in reverse genetic studies. Finally, we analyzed tumor metabolism and found that depending on the genetic background, some tumors undergo a lactogenic switch typical of the Warburg effect, while other tumors do not. In summary, this toolset allows for metabolic exploration of Drosophila tissues with spatial resolution and non-invasively, which could be useful for developmental and physiologic studies.