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The Drosophila Estrogen‐Related Receptor Coordinates Carbohydrate Metabolism with Developmental Growth
Author(s) -
Tennessen Jason M,
Baker Keith D,
Lam Geanette,
Evans Janelle,
Thummel Carl S
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.917.7
Subject(s) - biology , metabolic pathway , context (archaeology) , glycolysis , carbohydrate metabolism , microbiology and biotechnology , drosophila melanogaster , warburg effect , cell growth , receptor , metabolism , gene , biochemistry , paleontology
Drosophila larval metabolism is tuned to promote exponential growth in response to environmental nutrients. We have discovered that the metabolic program required for larval growth is established by the Drosophila Estrogen‐Related Receptor ( dERR ), the sole Drosophila ortholog of the vertebrate ERR nuclear receptor subclass. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triglyceride stores, and elevated levels of circulating sugars. These defects can be attributed to reduced expression of key genes in several metabolic pathways, including all of the genes that act in glycolysis. dERR appears to directly regulate of these pathways, as there are predicted dERR binding sites in nearly all of the misregulated genes examined. Intriguingly, the metabolic pathways induced by dERR at the onset of larval development are similar to those involved in the Warburg effect, by which cancer cells use glucose to support biomass production and proliferation. Our results demonstrate that the Warburg effect can be utilized in the context of normal developmental growth, indicate that dERR establishes the metabolic state that supports larval development, and implicate the ERR family as key regulators of the metabolic parameters that sustain cell proliferation and cancer progression. This work was supported by the NIH (1R01DK075607). JMT was supported by the NIDDK (F32DK083864).