Drosophila melanogaster activating transcription factor 4 regulates glycolysis during endoplasmic reticulum stress.
Bottom Line: The unfolded protein response transcription factor Atf4 was necessary for the up-regulation of glycolytic enzymes and Lactate dehydrogenase (Ldh).Finally, flies up-regulated Ldh and produced more lactate when subjected to ER stress.Together, these results suggest that Atf4 mediates a shift from a metabolism based on oxidative phosphorylation to one more heavily reliant on glycolysis, reminiscent of aerobic glycolysis or the Warburg effect observed in cancer and other proliferative cells.
Affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112.Show MeSH
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Mentions: To confirm these findings and to determine whether the expression changes were specific to DTT or a general response to ER stress, we treated S2 cells with another ER stress reagent, Tm (5 μg/mL), which inhibits N-linked glycosylation. We then monitored RNA levels of several genes over time, by qPCR (Figure 2). Consistent with the microarray results, expression of glycolytic genes and Ldh was increased and expression of genes encoding TCA cycle enzymes and respiratory chain complexes was decreased in response to Tm.
Affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112.