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: The metabolic gene expression changes described above suggest a switch from an OXPHOS-based metabolic state to a more glycolytic one. Because OXPHOS is the main oxygen-consuming process in most cells, such a shift would be characterized by reduced oxygen consumption and an increase in lactate production, as pyruvate is converted to lactate rather than imported into the mitochondria (Wu et al. 2007). Surprisingly, neither oxygen consumption nor lactate concentration in the culture media was changed upon treatment of S2 cells with ER stress-inducing agents (Figure 6). Because this lack of effect might be due to the in vitro nature of the experimental system, we decided to test whether metabolic gene expression changes occur in vivo and whether they are mirrored by changes in actual metabolism.
Affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112.