The Drosophila Estrogen-Related Receptor Directs a Metabolic Switch that Supports Developmental Growth

SummaryMetabolism must be coordinated with development to provide the appropriate energetic needs for each stage in the life cycle. Little is known, however, about how this temporal control is achieved. Here, we show that the Drosophila ortholog of the estrogen-related receptor (ERR) family of nuclear receptors directs a critical metabolic transition during development. dERR mutants die as larvae with low ATP levels and elevated levels of circulating sugars. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program normally associated with proliferating cells, supporting the dramatic growth that occurs during larval development. This study shows that dERR plays a central role in carbohydrate metabolism, demonstrates that a proliferative metabolic program is used in normal developmental growth, and provides a molecular context to understand the close association between mammalian ERR family members and cancer.

► dERR is required for the expression of genes involved in carbohydrate metabolism
► dERR triggers a developmentally programmed metabolic switch
► dERR promotes a form of aerobic glycolysis related to the Warburg effect
► A proliferative metabolic state can be used to support normal developmental growth